Inhibition of hairless protein mRNA

ABSTRACT

Methods for inhibition of hairless protein mRNA using RNA interference is described, in particular methods for hair removal. Also described are nucleic acid constructs for RNAi-mediated inhibition of hairless protein mRNA and compositions including such constructs.

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/113,423 filed Apr. 22, 2005, which is based on U.S. ProvisionalApplication Ser. No. 60/565,127 filed Apr. 23, 2004, the contents ofeach of which are incorporated by reference herein, and to each of whichpriority is claimed.

Sequence Listing

The sequence listing, submitted in duplicate on compact disk (CD), inlieu of a paper copy in compliance with 37 C.F.R. §§ 1.821(c) and1.52(e), and in duplicate on CD (CRF copy), in compliance with 37 C.F.R.§ 1.821 (e) has been generated from the specification and figures anddoes not constitute new matter. The Sequence Listing has been preparedusing FastSeq for Windows Version 4.0 software. Four identical CDs,labeled COPY 1, COPY 2, CRF of Sequence Listing submitted under 37C.F.R. § 1.821(e)—COPY 1 and CRF of Sequence Listing submitted under 37C.F.R. § 1.821(e) —COPY 2, (total four (4) CDs), created on Apr. 22,2005 each contain file: “AP36462_SEQLIST.TXT”, of size 2.28 MB(2,398,842 bytes). The specification incorporates herein by reference,the CD copies of the Sequence Listing submitted under 37 C.F.R §§1.821(c) and 1.52(e). The sequence listing, submitted herein, does notextend beyond the scope of the specification, and thus, does not containnew matter.

BACKGROUND OF THE INVENTION

The following is a discussion of some relevant art relating to hairlessprotein, and to RNAi. This discussion is provided only to assist theunderstanding of the reader, and does not constitute an admission thatany of the information provided or references cited constitutes priorart to the present invention.

As described in Christiano et al., PCT/US99/02128, WO 99/38965, Thehuman hair follicle is a dynamic structure which generates hair througha complex and highly regulated cycle of growth and remodeling. Hardy,1992, Trends Genet. 8:159; Rosenquist and Martin, 1996, Dev. Dynamics205:379. Hair growth is typically described as having three distinctphases. In the first phase, knows as anagen, the follicle is generatedand new hair grows.

During the second phase, known as catagen, the follicle enters the stagewhere elongation ceases and the follicle regresses because the matrixcells stop proliferating. At this stage, the lower, transient half ofthe follicle is eliminated due to terminal differentiation andkeratinization, and programmed cell death. Rosenquist and Martin, 1996,Dev. Dynamics 205:379. Also during catagen, although the dermal papillaremains intact, it undergoes several remodeling events, includingdegradation of the extracellular matrix that is deposited during anagen.At the close of catagen, the hair is only loosely anchored in a matrixof keratin, with the dermal papilla located just below. The catagenstage occurs at a genetically predetermined time, which is specific foreach hair type in a species.

The third phase, known as telogen, is characterized by the follicleentering a quiescent phase, during which the hair is usually shed. Whena new hair cycle is initiated, it is thought that a signal from thedermal papilla stimulates the stem cells, which are thought to reside inthe permanent portion of the follicle, to undergo a phase of downwardproliferation and genesis of a new bulbous base containing matrix cellswhich then surround the dermal papilla. As the new anagen stateprogresses, these hair matrix cells produce a new hair, the cycle beginsagain. Each follicle appears to be under completely asynchronouscontrol, resulting in a continuum of follicles in anagen, catagen, andtelegen phases, leading to a relatively homogeneous hair distribution.Hardy, 1992, Trends Genet. 8:159; Rosenquist and Martin, 1996, Dev.Dynamics 205:379.

Christiano et al., PCT/US99/02128, WO 99/38965 describes isolatednucleic acid encoding human hairless protein, the isolated protein, andmethods for identifying a compound that is capable of enhancing orinhibiting expression of a human hairless protein, and states that “Atherapeutic approach using antisense to human hairless can be used todirectly interfere with the translation of Human hairless proteinmessenger RNA into protein.” It further states that “antisense nucleicacid or ribozymes could be used to bind to the Human hairless proteinmRNA or to cleave it.”

Thompson, U.S. Pat. No. 6,348,348, issued Feb. 19, 2002, describes humanhairless gene and protein, and screening methods to identify agents thataffect expression of the human hairless gene.

Christiano, U.S. patent application Ser. No. 10/122,013, publication20030077614 (and corresponding Internation Application PCT/US02/11683,WO 02/083891), indicates that “The present invention provides DNAzymesand ribozymes that specifically cleave Hairless Protein mRNA.” Thepresent invention also provides antisense oligonucleotides thatspecifically inhibit translation of Hairless Protein mRNA. (Abstract.)Also, it states that “This invention provides a nucleic acid moleculethat specifically hybridizes to Hairless Protein mRNA so as to inhibitthe translation thereof in a cell”; (Specification 0099) and that“Antisense oligodeoxynucleotides were synthesized as directed to theinhibition of Hairless expression based on the Hairless mRNA sequence.”

SUMMARY OF THE INVENTION

The present invention concerns the use of RNA interference (RNAi) toinhibit mRNA's involved in hair growth, resulting in inhibition of hairgrowth. For many applications, short interfering RNA (siRNA) are used.Thus, inhibition of hairless protein mRNA, particularly during catagenphase, can result in permanent or at least long term inhibition of hairgrowth, and thus provides a method for hair removal. Consequently,inhibition of hairless protein mRNA can be used for hair removal and/orhair growth inhibition in cosmetic, therapeutic, and industrialapplications.

Thus, in a first aspect, the invention provides a method for hairremoval from a mammal, e.g., a human. The method involves applying to ahuman in an area comprising hair follicles a double stranded nucleicacid molecule that includes a sequence of at least a portion of humanhairless protein mRNA and a sequence complementary thereto.

In particular embodiments, the inhibition of hair growth in the treatedarea persists at least 1, 2, 4, 6, 8, 10, 12, or 24 months, or longer,or permanently.

In certain embodiments, the method also involves synchronizing hairgrowth cycles for hair follicles in the treated area, e.g., byextracting hairs such as by waxing. Such extraction causes follicles inanagen to transition into catagen thereby making those folliclessusceptible to inhibition using this invention, and triggers new hairgrowth of follicles in telogen and thus makes those follicles suitablefor transitioning into catagen. Thus, these methods synchronize hairfollicles in the hair cycle.

As used in connection with this invention, the term “hair removal”refers to physical removal and continuing inhibition of hair growth fromone or more hair follicles. Typically the hair removal applies to aplurality of hair follicles in a skin area on a subject. For example,the area can be up to 2, 5, 10, 20, 50, 100, 200, 400, or more cm². Forhair removal in an area, the hair removal may apply to all or a fractionof the hair follicles in the area.

The term “hair follicle” is used conventionally to refer to a biologicalhair producing structure.

As used in connection with the present methods, the term “applying”indicates that a substance is placed such that the substance isphysically present on or in an area.

The term “nucleic acid molecule” refers to a polymer that includes aplurality of linked nucleotides or nucleotide analogs, and may includeone or more modified internucleotidic linkages.

The term “hairless gene” refers to a mammalian gene that corresponds toreference human cDNA GenBank reference number NM_(—)005144, FIG. 1 (SEQID NO: 11412) and version NM_(—)005144.3, GI:62750351, FIG. 2 (SEQ IDNO:11413), recognizing that polymorphisms and potentially sequencingerrors may be present, or a species homolog of that sequence, e.g.,mouse homolog cDNA sequence NM_(—)021877.

Similarly the terms “hairless protein mRNA” and “hairless mRNA” refer toan mRNA encoding a hairless gene protein, and “human hairless mRNA”refers to a human homolog of such mRNA.

The phrase “inhibition of hair growth” is used to refer to a reductionor stoppage of hair growth caused at least in part by an agent notnormally present in cells in a hair follicle.

As used herein, the phrase “synchronizing hair growth cycles” means thatat least 10% of hair follicles in catagen or telogen phase in aparticular area are caused to enter anagen phase essentiallysimultaneously (i.e., within 2 weeks). Such synchronizing can beaccomplished, for example, with a physical action such as hairextraction or with one or more chemical or biomolecular agents.

As used herein, the term “hair extraction” refers to pulling ofindividual hair shafts out of their follicles.

A related aspect concerns a method for hair removal from an area of amammal comprising hair follicles, where the method involves applying tothe area a composition that includes at least one double strandednucleic acid molecule able to inhibit hairless mRNA translation invitro.

In certain embodiments, the method also includes synchronizing hairgrowth cycles for hair follicles in the treated area, such as by hairextraction, e.g., using waxing; the mammal is a human; the mammal is amouse; the mammal is a rat; the mammal is a bovine.

In another aspect, the invention provides a method of inhibitingexpression of hairless protein in a mammal. The method involvesadministering a double stranded nucleic acid molecule to the mammal,where the double stranded nucleic acid molecule includes a sequenceselected from the group consisting of oligonucleotides 1-5664 and theirrespective antisense sequences, or the species homology of suchsequences, and a sequence complementary thereto.

As used in the context of this invention, the term “inhibitingexpression” indicates that the level of mRNA and/or correspondingprotein or rate of production of the corresponding protein in a cellthat would otherwise produce the mRNA and/or protein is reduced ascompared to a non-inhibited but otherwise equivalent cell. Reduction inthe rate of production can be at various levels, including stopping suchproduction.

The term “species homolog” refers to a form of a gene, or correspondingnucleic acid molecule, or polypeptide from a particular species that issufficiently similar in sequence to the gene, corresponding nucleicacid, or polypeptide from a reference species that one skilled in theart recognizes a common evolutionary origin.

Thus, as used in connection with a molecule or composition, the phrase“able to inhibit hairless mRNA translation” indicates that the moleculeor composition has the property that when present in a cell that wouldtranslate hairless mRNA to produce protein in the absence of aninhibitor, the molecule or composition reduces the rate of biosynthesisof hairless protein (or even eliminate such biosynthesis). Suchreduction can occur in various ways, for example, by reducing the amountof mRNA available for translation or by at least partially blockingtranslation of mRNA that is present.

Reference to Oligonucleotides by number utilizes the oligonucleotidenumbering in Table 1, and therefore, specifies a nucleotide sequence.

In particular embodiments, the mammal is a human, a mouse, a rat, abovine (such as a cow), an ovine (such as a sheep), a monkey, a porcine(such as domestic pig).

The term “bovine” is used conventionally to refer to cattle, oxen, andclosely related ruminants.

Another aspect concerns a method for treating a human desirous of losinghair. The method involves administering to the human a composition thatincludes a double stranded nucleic acid molecule that includes asequence of at least a portion of human hairless protein mRNA and asequence complementary thereto.

As used herein, the phrase “desirous of losing hair” refers to anobjective indication of consent or request for a process to remove hairfrom a body area in a manner reducing or eliminating future hair growthin that area for a period of time, e.g., at least 1 week, 2 weeks, 1month, 2 months, or longer.

A further aspect concerns a method for marketing a composition for hairremoval, which includes providing for sale to medical practitioners(e.g., doctors, nurse practitioners, doctor's assistants, and nurses) orto the public (e.g., spas and other body care businesses, andindividuals) a packaged pharmaceutical composition that includes adouble stranded nucleic acid molecule containing a sequence of at leasta portion of human hairless protein mRNA and a sequence complementarythereto; and a package label or insert indicating that thepharmaceutical composition can be used for hair removal.

In particular embodiments, the pharmaceutical composition is approved bythe U.S. Food and Drug Administration, and/or by an equivalentregulatory agency in Europe or Japan, for hair removal in humans; thepharmaceutical composition is packaged with a hair removal wax or othercomponent adapted for hair removal.

The term “pharmaceutical composition” refers to a substance thatcontains at least one biologically active component. The compositiontypically also contains at least one pharmaceutically acceptable carrieror excipient.

As used herein, the term “packaged” means that the referenced materialor composition is enclosed in a container or containers in a mannersuitable for storage or transportation. For example, a pharmaceuticalcomposition may be sealed in a vial, bottle, tube, or the like, whichmay itself be inside a box. Typically, a label on the containeridentifies the contents and may also provide instructions for use and/orcautions to prevent misuse.

The term “hair removal wax” refers to refer to a substance that isadapted for removal of hair by embedding hair in the substance and thenpulling the material away, thereby pulling embedded hairs out of thehair follicles. The substance may be used with a backing material suchas paper or cloth. Both hot and cold waxes are commonly available.Unless clearly indicated, the term is not limited to substances that arechemically waxes; for example, the term will generally includesubstances such as caramel-based substances that are used for“sugaring”.

The term “other component adapted for hair removal” refers to a materialor device that can be used for physically removing hairs and is eithergenerally recognized as suitable for such use, of instructions areprovided indicating that the component can be used for physical hairremoval or providing instructions on performing such removal.

Another aspect concerns an isolated double stranded nucleic acidmolecule that includes a nucleotide sequence corresponding to 19-25contiguous nucleotides from human hairless mRNA, where the nucleotidesequence contains a nucleotide sequence selected from the groupconsisting of oligonucleotides 1-5664; and a nucleotide sequencecomplementary thereto, where the double stranded nucleic acid moleculeinduces RNA interference in a human cell in vitro.

Indication that a molecule or material of interest “induces RNAinterference in a human cell in vitro” means that when present incultured cells that are capable of RNA interference and under conditionssuch that a molecule or molecules that will normally induce RNAinterference do induce RNAi in the cell, the molecule or material ofinterest will induce such RNA interference.

Likewise, in another aspect the invention provides a pharmaceuticalcomposition that includes a double stranded nucleic acid molecule thatcontains a nucleotide sequence corresponding to 14-50, 17-40, 17-30,17-25, 19-30, 19-29, 19-28, 19-26, 19-25, 19-24, 19-23, 20-23, 20-22, or21-22 contiguous nucleotides from human hairless mRNA including anucleotide sequence selected from the group consisting ofoligonucleotides 1-5664, and a sequence complementary thereto, whereinsaid double stranded nucleic acid molecule induces RNA interference in ahuman cell in vitro.

In yet another aspect, the invention provides a kit that includes apharmaceutical composition that contains a double stranded nucleic acidmolecule that includes a sequence of at least a portion of humanhairless protein mRNA and a sequence complementary thereto; and apackage label or insert indicating that said pharmaceutical compositioncan be used for hair removal.

In certain embodiments, the kit is approved by the U.S. Food and DrugAdministration or equivalent regulatory agency in Europe or Japan, forhuman hair removal.

In certain embodiments of the above aspects or other aspects describedherein, the double stranded nucleic acid includes at least one (i.e.,one or two) 3′-overhang, e.g., a 1, 2, or 3 nucleotide overhang. Incertain embodiments, such overhang includes one or morenon-ribonucleotides; includes 1, 2, or 3 deoxynucleotide; includes amodified linkage; each strand has a 1, 2, or 3 nucleotide overhang.

In certain embodiments of the above aspects, at least one strand of thedouble stranded nucleic acid includes at least one nucleotide analog orinternucleotidic linkage different from unmodified RNA; each strandincludes at least one nucleotide analog or internucleotidic linkagedifferent from unmodified RNA; at least one strand includes at least onemodified nucleotide; each strand includes at least one modifiednucleotide.

In certain embodiments of the above aspects, the double stranded nucleicacid molecule induces RNA interference in a cell in vitro and includesthe RNA sense sequence of Oligonucleotide 131, namely5′-CUCUCCAGACAUUUGGCAA-3′ (SEQ ID NO: 11329), and its complementary RNAsequence 5′-TTGCCAAATGTCTGGAGAG-3′ (SEQ ID NO:262); includes the RNAsense sequence of Oligonucleotide 1194, namely 5′-GUGCGGCCGAUCCGCGCCG-3′(SEQ ID NO: 11330), and its complementary RNA sequence5′-CGGCGCGGAUCGGCCGCAC-3′ (SEQ ID NO:11331); includes the RNA sensesequence of Oligonucleotide 1521, namely 5′-TGGGAGAAGACGGCCCCAG-3′ (SEQID NO:3041) its complementary RNA sequence 5′-CTGGGGCCGTCTTCTCCCA-3′(SEQ ID NO: 3042); includes an RNA sense sequence and a complementaryRNA antisense sequence selected from the group consisting ofoligonucleotides 1-5664; is targeted to hairless mRNA corresponding to asite in the coding sequence (CDS) covering nucleotides 1482 to 5051;includes a nucleotide sequence corresponding to an oligonucleotideselected from Oligonucleotides 1482 to 5032; includes a nucleotidesequence corresponding to an oligonucleotide selected fromOligonucleotides 1482 to 4032; includes a nucleotide sequencecorresponding to an oligonucleotide selected from Oligonucleotides 1482to 3032; includes a nucleotide sequence corresponding to anoligonucleotide selected from Oligonucleotides 1482 to 2032; includes anucleotide sequence corresponding to an oligonucleotide selected fromOligonucleotides 1582 to 1732.

In certain embodiments of the above aspects, in the double strandednucleic acid molecule, the sense sequence and the antisense sequenceeach include 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 complementarynucleotides and 1 to 3 non-complementary 3′-nucleotides.

In certain embodiments of the above aspects, chemically modified nucleicacids are used, e.g., chemically modified siRNAs (siNAs) as described inMcSwiggen et al., PCT/US03/05346, WO 03/070918, which is incorporatedherein by reference.

As used herein, the terms “siRNA” and “siNA” both refer to doublestranded nucleic acid that induces RNAi, and includes unmodified RNAoligonucleotides and chemically modified oligonucleotides. Whenunmodified RNA is intended, the term “unmodified RNA” is expressly used.

The term “RNAi inducing oligonucleotide” or “RNA interference inducingoligonucleotide” refers to an oligonucleotide, generally a doublestranded molecule (usually an siRNA molecule), that is able to induceRNA interference in a suitable cell.

In certain embodiments of the above aspects involving application of thepresent oligonucleotides to a mammal, the oligonucleotides are appliedat 0.01 to 0.1 microgram/cm², 0.1 to 0.2 microgram/cm², 0.2 to 0.5microgram/cm², 0.5 to 1.0 microgram/cm², 1.0 to 2.0 microgram/cm², 2.0to 5.0 microgram/cm², or 5.0 to 10.0 microgram/cm²; a combination ofdifferent RNAi inducing oligonucleotides is applied, which applicationcan be as a mixture or mixtures or separately, e.g., 2, 3, 4, 5, 6, 7,8, 9, 10, or more different oligonucleotides; one or more different RNAiinducing oligonucleotides (e.g., all targeted to hairless, e.g., siRNA)is applied in combination (as a mixture or separately) with one or moredifferent agents that inhibit hairless translation or hairless activity;one or more different RNAi inducing oligonucleotides is applied incombination with one or more other hair removal agents, such as chemicaldepilatories and/or enzymatic hair removal agents. In accordance withthe preceding description of embodiments, certain of the presentpharmaceutical compositions also include at least one hairlessinhibiting agent different from an RNAi inducing agent, at least onechemical depilatory; at least one enzymatic hair removal agent.

In certain embodiments, the present RNAi inducing oligonucleotides areapplied once; applied daily for at least 7 days; applied daily for atleast 14 days; applied on at least 4 days within a one month period;applied on at least 7 days within a one month period; applied at least 4days per week for at least a four week period.

In particular embodiments, the RNAi inducing oligonucleotide does notinclude the sequence of a siRNA as shown in the Examples; the RNAioligonucleotide includes the sequence of an siRNA shown in the Examplesand the method of use includes synchronizing hair cycles, e.g., asdescribed herein.

In particular embodiments involving mammalian mRNAs, the RNAi inducingoligonucleotide (e.g., siRNA) includes a sequence 17, 18, 19, 20, 21,22, 23, 24, or 25 nucleotides in length (or at least one of thoselengths) of one of the sequences shown in Table 3, or a sequencecomplementary thereto; the RNAi inducing oligonucleotide targets amammalian hairless mRNA sequence corresponding to a sequence shown inTable 3.

In particular embodiments, the RNAi inducing oligonucleotide (e.g.,siRNA) targets a human hairless mRNA sequence as identified in Table 4;the RNAi inducing oligonucleotide contains a sequence of 17, 18, 19, 20,21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length (or atleast one of those lengths).

In particular embodiments, the RNAi inducing oligonucleotide (e.g.,siRNA) targets a mouse hairless mRNA sequence as identified in Table 5;the RNAi inducing oligonucleotide contains a sequence of 17, 18, 19, 20,21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length (or atleast one of those lengths).

Additional embodiments will be apparent from the Detailed Descriptionand from the claims.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1. NM005144 (SEQ ID NO:11412)

FIG. 2. NM005144.3 (SEQ ID NO: 11413)

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention concerns methods for inhibiting hair growth, byinhibiting particular mRNAs using RNAi, e.g., using siRNA. In particularnon-limiting embodiments, the present invention provides for siRNAmolecules, e.g., double stranded RNA oligonucleotides (which optionallymay be chemically modified and/or comprise at least one 3′ overhang, asset forth below), comprising a nucleotide sequence that is complementaryto a target nucleotide sequence which may be 17, 18, 19, 20, 21, 22, 23,24 or 25 nucleotides in length, where the siRNA contains a sequence 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 base pairs inlength. Preferably, the hairless in RNA target nucleotide sequencecomprises a 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleotide portion ofthe human hairless mRNA sequence set forth in FIG. 1 (SEQ ID NO: 11412)and/or FIG. 2 (SEQ ID NO: 11413). Non-limiting examples of targetsequences may be identified as loops identified in secondary mRNAstructure using software designed for such purpose (e.g. RnaDraw,RnaMotif, Rnaview-RnaMLView, RnaViz, Vienna RNA Package, etc.).

A. RNAi and siRNA

RNA interference (RNAi) refers to the process of sequence-specificpost-transcriptional gene silencing in animals mediated by shortinterfering RNAs (siRNAs) (Fire et al., 1998, Nature, 391, 806). Thecorresponding process in plants is commonly referred to aspost-transcriptional gene silencing or RNA silencing and is alsoreferred to as quelling in fungi. The process of post-transcriptionalgene silencing is thought to be an evolutionarily-conserved cellulardefense mechanism used to prevent the expression of foreign genes and iscommonly shared by diverse flora and phyla (Fire et al., 1999, TrendsGenet., 15, 358). The presence of dsRNA in cells triggers the RNAiresponse though a mechanism that appears to be different from theinterferon response that results from dsRNA-mediated activation ofprotein kinase PKR and 2′,5′-oligoadenylate synthetase resulting innon-specific cleavage of mRNA by ribonuclease L.

The presence of long dsRNAs in cells stimulates the activity of theenzyme, dicer, a ribonuclease III. Dicer is involved in the processingof the dsRNA into short pieces of dsRNA known as short interfering RNAs(siRNAs) (Berstein et al., 2001, Nature, 409, 363). The resulting RNAsare typically about 21 to about 23 nucleotides in length, withcomplementary sequences of about 19 base pairs. Dicer has also beenimplicated in the excision of 21- and 22-nucleotide small temporal RNAs(stRNAs) from precursor RNA of conserved structure that are implicatedin translational control (Hutvagner et al., 2001, Science, 293, 834).The RNAi response also involves an endonuclease complex, commonlyreferred to as an RNA-induced silencing complex (RISC), which mediatescleavage of single-stranded RNA having sequence complementary to theantisense strand of the siRNA duplex. Cleavage of the target RNA takesplace in the middle of the region complementary to the antisense strandof the siRNA duplex (Elbashir et al., 2001, Genes Dev., 15, 188).

RNAi has been studied in a variety of systems. Fire et al., 1998,Nature, 391, 806, described RNAi in C. elegans. Wianny and Goetz, 1999,Nature Cell Biol., 2, 70, describe RNAi mediated by dsRNA in mouseembryos. Hammond et al., 2000, Nature, 404, 293, describe RNAi inDrosophila cells transfected with dsRNA. Elbashir et al., 2001, Nature,411, 494, describe RNAi induced by introduction of duplexes of synthetic21-nucleotide RNAs in cultured mammalian cells including human embryonickidney and HeLa cells.

Work in Drosophila embryonic lysates (Elbashir et al., 2001, EMBO J, 20,6877) has revealed certain factors of siRNA length, structure, chemicalcomposition, and sequence that are significantly affect efficient RNAiactivity. These studies have shown that 21-nucleotide siRNA duplexes aremost active when containing 3′-terminal nucleotide overhangs.Furthermore, complete substitution of one or both siRNA strands with2′-deoxy (2′-H) or 2′-O-methyl nucleotides abolishes RNAi activity,whereas substitution of the 3′-terminal siRNA overhang nucleotides with2′-deoxy nucleotides (2′-H) was shown to be tolerated. Single mismatchsequences in the center of the siRNA duplex were also shown to abolishRNAi activity. In addition, these studies also indicate that theposition of the cleavage site in the target RNA is defined by the 5′-endof the siRNA guide sequence rather than the 3′-end of the guide sequence(Elbashir et al., 2001, EMBO J., 20, 6877). Other studies have suggestedthat a 5′-phosphate on the target-complementary strand of a siRNA duplexis important for siRNA activity and that ATP is utilized to maintain the5′-phosphate moiety on the siRNA (Nykanen et al., 2001, Cell, 107, 309).

Studies have shown that replacing the 3′-terminal nucleotide overhangingsegments of a 21-mer siRNA duplex having two 2-nucleotide 3′-overhangswith deoxyribonucleotides does not have an adverse effect on RNAiactivity. Replacing up to 4 nucleotides on each end of the siRNA withdeoxyribonucleotides has been reported to be well-tolerated whereascomplete substitution with deoxyribonucleotides results in no RNAiactivity, but that substitution of siRNA with 2′-O-methyl nucleotidescompletely abolishes RNAi activity. (Elbashir et al., 2001, EMBO J., 20,6877.)

Li et al., International PCT Publication No. WO 00/44914, and Beach etal., International PCT Publication No. WO 01/68836 both suggest thatsiRNA “may include modifications to either the phosphate-sugar backboneor the nucleoside . . . to include at least one of a nitrogen or sulfurheteroatom.”

Kreutzer and Limmer, Canadian Patent Application No. 2,359,180, alsodescribe certain chemical modifications for use in dsRNA constructs inorder to counteract activation of double-stranded RNA-dependent proteinkinase PKR, specifically 2′-amino or 2′-O-methyl nucleotides, andnucleotides containing a 2′-O or 4′-C methylene bridge

Parrish et al., 2000, Molecular Cell, 6, 1977-1087, tested certainchemical modifications targeting the unc-22 gene in C. elegans usinglong (>25 nt) siRNA transcripts. The authors describe the introductionof thiophosphate residues into these siRNA transcripts by incorporatingthiophosphate nucleotide analogs with T7 and T3 RNA polymerase andobserved that “RNAs with two [phosphorothioate] modified bases also hadsubstantial decreases in effectiveness as RNAi triggers (data notshown); [phosphorothioate] modification of more than two residuesgreatly destabilized the RNAs in vitro and we were not able to assayinterference activities.” Id. at 1081. The authors also tested certainmodifications at the 2′-position of the nucleotide sugar in the longsiRNA transcripts and observed that substituting deoxynucleotides forribonucleotides “produced a substantial decrease in interferenceactivity,” especially in the case of Uridine to Thymidine and/orCytidine to deoxy-Cytidine substitutions. Id. In addition, the authorstested certain base modifications, including substituting, in sense andantisense strands of the siRNA, 4-thiouracil, 5-bromouracil,5-iodouracil, and 3-(aminoallyl)uracil for uracil, and inosine forguanosine. They found that whereas 4-thiouracil and 5-bromouracil wereall well-tolerated, inosine “produced a substantial decrease ininterference activity” when incorporated in either strand. Incorporationof 5-iodouracil and 3-(aminoallyl)uracil in the antisense strandresulted in substantial decrease in RNAi activity as well.

Beach et al., International PCT Publication No. WO 01/68836, describesspecific methods for attenuating gene expression usingendogenously-derived dsRNA.

Tuschl et al., International PCT Publication No. WO 01/75164, describe aDrosophila in vitro RNAi system and the use of specific siRNA moleculesfor certain functional genomic and certain therapeutic applications;although Tuschl, 2001, Chem. Biochem., 2, 239-245, doubts that RNAi canbe used to cure genetic diseases or viral infection due “to the dangerof activating interferon response.”

Li et al., International PCT Publication No. WO 00/44914, describe theuse of specific dsRNAs for use in attenuating the expression of certaintarget genes.

Zernicka-Goetz et al., International PCT Publication No. WO 01/36646,describe certain methods for inhibiting the expression of particulargenes in mammalian cells using certain dsRNA molecules.

Fire et al., International PCT Publication No. WO 99/32619, describeparticular methods for introducing certain dsRNA molecules into cellsfor use in inhibiting gene expression.

Plaetinck et al., International PCT Publication No. WO 00/01846,describe certain methods for identifying specific genes responsible forconferring a particular phenotype in a cell using specific dsRNAmolecules.

Mello et al., International PCT Publication No. WO 01/29058, describethe identification of specific genes involved in dsRNA-mediated RNAi.

Deschamps Depaillette et al., International PCT Publication No. WO99/07409, describe specific compositions consisting of particular dsRNAmolecules combined with certain anti-viral agents.

Waterhouse et al., International PCT Publication No. 99/53050, describecertain methods for decreasing the phenotypic expression of a nucleicacid in plant cells.

Driscoll et al., International PCT Publication No. WO 01/49844, describespecific DNA constructs for use in facilitating gene silencing intargeted organisms.

Parrish et al., 2000, Molecular Cell, 6, 1977-1087, describe specificchemically-modified siRNA constructs targeting the unc-22 gene of C.elegans.

Grossniklaus, International PCT Publication No. WO 01/38551, describescertain methods for regulating polycomb gene expression in plants.

Churikov et al., International PCT Publication No. WO 01/42443, describecertain methods for modifying genetic characteristics of an organism.

Cogoni et al., International PCT Publication No. WO 01/53475, describecertain methods for isolating a Neurospora silencing gene and usesthereof.

Reed et al., International PCT Publication No. WO 01/68836, describecertain methods for gene silencing in plants.

Honer et al., International PCT Publication No. WO 01/70944, describecertain methods of drug screening using transgenic nematodes asParkinson's Disease models.

Deak et al., International PCT Publication No. WO 01/72774, describecertain Drosophila-derived gene products.

Arndt et al., International PCT Publication No. WO 01/92513, describecertain methods for mediating gene suppression by using factors thatenhance RNAi.

Tuschl et al., International PCT Publication No. WO 02/44321, describecertain synthetic siRNA constructs.

Pachuk et al., International PCT Publication No. WO 00/63364, andSatishchandran et al., International PCT Publication No. WO 01/04313,describe certain methods and compositions for inhibiting the function ofcertain oligonucleotide sequences.

Echeverri et al., International PCT Publication No. WO 02/38805,describe certain C. elegans genes identified via RNAi.

Kreutzer et al., International PCT Publications Nos. WO 02/055692, WO02/055693, and EP 1144623 B1 describes certain methods for inhibitinggene expression using RNAi.

Graham et al., International PCT Publications Nos. WO 99/49029 and WO01/70949, and AU 4037501 describe certain vector expressed long doublestranded RNA molecules.

McSwiggen et al., PCT/US03/05028, WO 03/074654 describes RNAinterference mediated inhibition of gene expression using shortinterfering nucleic acid (siNA), and provides a table listing thousandsof mRNAs, which is believed to include hairless protein mRNA, aspotential targets for such siNA.

McSwiggen et al., PCT/US03/05346, WO 03/070918 describes syntheticchemically modified small nucleic acid molecules capable of mediatingRNA interference against target nucleic acid sequences. The referencereports that up to all of the nucleotides in the RNA strands can bereplaced with moieties that are not ribonucleotides.

B. Hairless Protein mRNA

Applicant's have found that RNAi can be used to inhibit translation fromhairless protein mRNA, resulting in hair removal. This hair removal islong term, or even permanent, thus providing cosmetic and therapeuticmethods, as well as methods useful for laboratory experimental mammals,and for de-hairing in the leather industry.

The Hairless Protein gene is expressed during a narrow window during thehair cycle, just at the transition to catagen (the regression phase).(Panteleyev et al. 1998, Exp Dermatol. 7:249-67; Panteleyev et al. 2000,Am J Pathol. 157:1071-9). In both humans and mice with mutations in thehairless gene, the cardinal finding is a wave of hair shedding shortlyafter birth, and no subsequent hair growth throughout life. Thephenotype results from permanent structural damage to the hair follicle,after which no further hair cycling can occur. In addition, humans andmice which are genetically deficient in hairless gene expression exhibitno other phenotypic manifestations or abnormalities that might beassociated with a deleterious effect (Zlotogorski et al., 2002, J InvestDermatol. 118:887-90), suggesting that hairless is specifically involvedand indispensable in regulating the hair cycle, and that its functionselsewhere in the body (if any) are compensated by other factors.

As a result, hair removal using RNAi targeted to hairless mRNA providesan advantageous approach, as any inadvertent, non-localized inhibitionof hairless mRNA will not adversely affect the subject.

C. Applications and Conditions to be Treated

As indicated above, the present invention concerns inhibition of hairgrowth, and consequent hair removal, and is applicable to a number ofdifferent therapeutic, cosmetic, and industrial applications. Themethods can be readily adapted to any of the various mammals havinghairless protein analogs, for example, human, mouse, rat, cattle (andother bovines), equines.

1. Long Term (Permanent) Hair Removal

Permanent, or at least long term, hair removal can involve inhibition ofhairless protein. Such hair removal is useful for both cosmetic andtherapeutic applications. Exemplary cosmetic applications can include,for example, back and chest hair for men and upper lip, eyebrow, leg,arm, underarm, and pubic hair for women.

In addition to cosmetic applications, permanent or long term hairremoval is also useful in certain conditions, e.g., trachoma, thevarious forms of hypertrichosis, and hirsutism.

Hypertrichosis

Hypertrichosis describes all forms of hair growth that are excessive forthe bodily location and age of an individual, and which do not resultfrom androgen stimulation. The present invention can be used for thevarious forms and causes of hypertrichosis, e.g., those describedherein.

Hypertrichosis is usually categorized on the basis of the age of onset(at birth or during later years), the extent of distribution (universalor localized), the site of involvement (elbows, anterior or posteriorneck), and the cause (genetic or acquired).

Acquired hypertrichosis may result from the use of particular drugs, forexample, oral minoxidil, phenyloin, and cyclosporin. Acquiredhypertrichosis lanuginosa may also be a manifestation of an underlyingmalignancy. In the dermatological literature, this is known as“malignant down”. Additional causes of acquired hypertrichosis includehormonal imbalances, malnutrition, HIV and local inflammation.

In addition, some forms of hypertrichosis are clearly hereditary but thegenes involved generally remain unknown. Genetic forms of hypertrichosisare very rare human disorders.

There are only a small number of human disorders that have generalizedcongenital hypertrichosis as the leading phenotypic feature. Theseinclude:

Hypertrichosis universalis (MIM145700)

Hypertrichosis universalis congenita, Ambras type (MIM145701)

Gingival fibromatosis with hypertrichosis (MIMI 35400)

Barber-Say syndrome (MIM209885)

Amaurosis congenita, cone-rod type, with hypertrichosis (MIM204110),

CAHMR syndrome (MIM21770)

Cantu syndrome (MIM239850)

Gingival fibromatosis with hypertrichosis and mental retardationMIM605400)

X-linked hypertrichosis (MIM307150)

Acromegaly and hypertrichosis (Irvine et al, 1996).

Of these, only Hypertrichosis universalis, Ambras type hypertrichosis,and X-linked hypertrichosis have excessive hair as the predominantfeature. In all the other listed syndromes hypertrichosis is associatedwith additional more prominent abnormalities. The present invention canbe used to treat hypertrichosis, e.g., in any of the conditions listedabove, as well as in other conditions in which trichosis occurs.

Trachoma

Trachoma is the leading cause of blindness worldwide. The World HealthOrganization estimates that there are 146 million people with trachomaand that the disease has caused blindness in 5.9 million people, 15% ofthe world's blindness. Trachoma is caused by the gram-negative bacteriumChlamydia trachomatis, an intracellular parasite transmitted by flyinfestation. In trachoma, the conjunctival lining of the eyelids becomesinfected with the bacterium, which over the long term, causes aninflammatory response. The inflammation can lead to scarring, shorteningof the lid and in-turning of the eyelashes. Trichiasis, the conditionwhen eyelashes rub on the cornea, can lead to blindness. An estimated10.6 million adults have inturned eyelashes that require surgery.

While it is advantageous of the Chlamydia infection is prevented, ortreated before in-turning of the eyelashes, there is a need fornon-surgical approaches to treatment that can at least reduce thecorneal scarring. Thus, removal of the eyelash hairs (without leavingstubble) using the present invention can substantially slow, or evenprevent such corneal damage, thereby preserving the individual's vision.

Trichiasis

In addition to trachoma, in-turned eyelashes (trichiasis) can have othercauses, and are a common source of recurrent ocular irritation for somepatients. The in-turned lash (or lashes) in contact with the conjunctivaand/or cornea may lead to a foreign body sensation, localizedconjunctival injection, pain and photophobia.

Trichiasis is the term used for misdirection or aberrant placement ofeyelashes along the eyelid margin resulting in lash growth toward thecornea. Trichiasis is an acquired condition that may be caused by thefollowing inflammatory or traumatic processes involving the eyelids. Thepresent invention can be used in all cases of trichiasis, includingthose in the following causal situations:

Chronic blepharitis with meibomianitis—chronic inflammatory changeswithin the tarsal plate and posterior eyelid margin may causedestruction and misdirection of lash follicles, resulting in chronictrichiasis.

Lid lacerations and thermal burns to the lid margin—may causeredirection of the lash roots with resultant trichiasis.

Previous surgery on eyelids—For example, lid adhesions (tarsorrhaphys)done to prevent exposure in some patients with seventh nerve palsies maycause misdirection of lashes. Similarly, in many reconstructive eyelidprocedures, the new eyelid margin may contain fine skin hairs(lanugo-type) that rub on the cornea.

Mucocutaneous diseases—Stevens-Johnson syndrome and Ocular CicatricialPemphigoid result not only in the destruction of the eyelid margins andtrichiasis but also in the formation of new lashes from the meibomiangland orifices (a condition referred to as distichiasis).

Other cicatricial conjunctival diseases—Herpes Simplex conjunctivitisand Herpes Zoster may cause a cicatrizing conjunctivitis withdestruction of the lid margin and lash follicles. Trachoma may alsocause a chronic tarsitis with cicatrizing conjunctivitis in the upper orlower eyelid and resultant trichiasis (as well as a cicatricialentropion).

Irradiation and chemical burns—Therapeutic irradiation for eyelidcancers or alkali burns may lead to a disruption of the normal eyelidmargin anatomy and resultant misdirection of eyelashes. Both of theseprocesses may also lead to metaplasia of squamous epithelium of themucocutaneous margin of the eyelid with resultant keratinization, asource of ocular irritation. In addition, destruction of the gobletcells, accessory lacrimal glands, and lacrimal gland will disrupt thenormal tear flow, compounding the above problems.

Other conditions in which eyelashes contact the cornea also exist, andthe present invention can be used in those cases also. For example:

A condition similar to trichiasis is Eyelid entropion—True entropion(e.g. involutional type seen in the aging population) is characterizedby a normal eyelid margin architecture: the eyelid inverts as a resultof eyelid laxity, allowing the eyelashes to rub on the cornea. Severalof the entities mentioned above (Ocular Pemphigoid, Stevens-JohnsonSyndrome) may cause a cicatrization of the conjunctiva as well as thelid margin and create a cicatricial entropion with trichiasis (i.e. theeyelid is inverted due to a cicatricial process). In addition, eyelashesmay be misdirected not only due to the lid position, but also due to theinflammatory process involving the actual lash follicles. Therefore,sometimes there may be two problems present (entropion and trichiasis)both of which may require treatment.

Epiblepharon—Epiblepharon is a congenital condition commonly seen in thelower Asian eyelid. A fold of skin and muscle roll upwards and pressesthe lashes toward the cornea. This does not represent true trichiasis.

Distichiasis—is an abnormality in which an aberrant second row oflashes, (usually from the meibomian gland orifices) grows behind thenormal lash line. It may be congenital or acquired. Any process causingchronic inflammation of the lid margin and meibomian glands maytransform the meibomian glands into pilosebaceous units capable ofproducing hair (e.g. chronic blepharitis).

Combined eyelid margin process—Several of the eyelid processes mentioned(Stevens-Johnson syndrome, Ocular Pemphigoid, irradiation, chemicalburns) not only may cause entropion and trichiasis, but in addition maylead to squamous metaplasia and keratinization of the non-keratinizingsquamous epithelium of the eyelid margin. Keratinized tissue is veryirritating to the eye. Therefore, several factors may contribute to theocular irritation, and as a result, several types of treatment could berequired.

Marginal entropion—Is a subtle form of entropion that is seen only atthe lid margin. Usually there is chronic inflammation at the eyelidmargin with a mild cicatricial process that is starting to roll the lidmargin inward. The eyelashes appear more vertical with some trulytrichiatic lashes. The clinical clue is the meibomian gland orifices.Normally they should be vertical and not covered by conjunctivalepithelium. If the openings are rolled inward and conjunctiva is growingover the opening, then marginal entropion is present in addition totrichiasis. It is important to distinguish this condition whenconsidering treatment.

Hirsutism

Hirsutism is excessive hair growth on a female in a male growth pattern,typically excessive facial hair. Hirsutism is usually caused by anincreased sensitivity of the skin to a group of hormones calledandrogens (testosterone and androstenedione) or increased production ofthese hormones. Androgen disorders (hyperandrogenism) affects between 5%to 10% of all women. Hair from this condition can be removed in full orpart using the present invention.

Pseudofolliculitis barbae

Pseudofolliculitis barbae (razor bumps) is a common condition of thebeard area occurring in African American men and other people with curlyhair. The problem results when highly curved hairs grow back into theskin causing inflammation and a foreign body reaction. Over time, thiscan cause keloidal scarring which looks like hard bumps of the beardarea and neck. Currently this is usually addressed by attempting toprevent the hair from curving back and growing into the skin withaltered shaving practices and the like. The present invention can beused to eliminate hairs causing such difficulties.

Experimental Animals

Permanent hair removal as described herein can also be used withexperimental animals to remove hair from all or a portion of the body ofan experimental animal. Thus, for example, a hairless spot can becreated on a mouse, rat, sheep, monkey, chimpanzee, rabbit or otheranimal for application over an extended period of time of topicallyapplied pharmaceutical compounds or other materials. Thus, the presentinvention can be used for this purpose, either with or without shavingshaveing, waxing, or depilation, or other such treatment. In some cases,the hairless spot or area on the animal is initially created withshaving, waxing, or other hair removal method, and the present inventionallows the bare area to be maintained (which may be after a sustainedperiod of application of the present compositions, e.g., at least 2, 4,7, or 10 days, or 2, 3, 4, 5, 6, 8, 10, 12, weeks or even longer).

Industrial Applications

In addition, permanent hair removal as described herein can also beuseful to remove hair from mammals whose hides will be used for leather.Dehairing is one of the main initial steps in leather production. Fivemethods of dehairing are commonly used: i.e., (i) clipping process, (ii)scalding process, (iii) chemical process, (iv) sweating process, and (v)enzymatic process. Of these, the most commonly practiced method ofdehairing of hides and skins is the chemical process using lime andsodium sulphide. However, the use of high concentrations of lime andsodium sulphide creates an extremely alkaline environment resulting inthe pulping of hair and its subsequent removal, and presents substantialpollution problems. Thus, removal of hairs using the present inventionallows hides to be prepared for leather production while eliminating orat least reducing the use of the pollution-causing methods.

D. Use of RNAi and Oligo Sequences

The use of RNAi to reduce or eliminate translation from a targeted mRNAhas been described in a number of patents and published patentapplications, e.g., as mentioned in the Background of the Invention. Inthe present invention, particular target sites in hairless protein mRNAcan be identified experimentally and/or using software programs toidentify accessible sites. For example, procedures such as thosedescribed below can be used to identify sites, and to select an optimalsite and active oligonucleotide.

Identification of Potential RNAi (e.g., siRNA) Target Sites in any RNASequence

The sequence of an RNA target of interest, such as a viral or human mRNAtranscript, is screened for target sites, for example by using acomputer folding algorithm. In a non-limiting example, the sequence of agene or RNA gene transcript derived from a database, such as Genbank, isused to generate siNA targets having complementarity to the target. Suchsequences can be obtained from a database, or can be determinedexperimentally as known in the art. Target sites that are known, forexample, those target sites determined to be effective target sitesbased on studies with other nucleic acid molecules, for exampleribozymes or antisense, or those targets known to be associated with adisease or condition such as those sites containing mutations ordeletions, can be used to design siNA molecules targeting those sites aswell. Various parameters can be used to determine which sites are themost suitable target sites within the target RNA sequence. Theseparameters include but are not limited to secondary or tertiary RNAstructure, the nucleotide base composition of the target sequence, thedegree of homology between various regions of the target sequence, orthe relative position of the target sequence within the RNA transcript.Based on these determinations, any number of target sites within the RNAtranscript can be chosen to screen siNA molecules for efficacy, forexample by using in vitro RNA cleavage assays, cell culture, or animalmodels. In a non-limiting example, anywhere from 1 to 1000 target sitesare chosen within the transcript based on the size of the siNA constructto be used. High throughput screening assays can be developed forscreening siNA molecules using methods known in the art, such as withmulti-well or multi-plate assays or combinatorial/siNA library screeningassays to determine efficient reduction in target gene expression.

Selection of siNA Molecule Target Sites in a RNA

The following non-limiting steps can be used to carry out the selectionof siNAs targeting a given gene sequence or transcript.

-   -   1 The target sequence is parsed in silico into a list of all        fragments or subsequences of a particular length, for example 23        nucleotide fragments, contained within the target sequence. This        step is typically carried out using a custom Perl script, but        commercial sequence analysis programs such as Oligo, MacVector,        or the GCG Wisconsin Package can be employed as well.    -   2 In some instances the siNAs correspond to more than one target        sequence; such would be the case for example in targeting        different transcripts of the same gene, targeting different        transcripts of more than one gene, or for targeting both the        human gene and an animal homolog. In this case, a subsequence        list of a particular length is generated for each of the        targets, and then the lists are compared to find matching        sequences in each list. The subsequences are then ranked        according to the number of target sequences that contain the        given subsequence; the goal is to find subsequences that are        present in most or all of the target sequences. Alternately, the        ranking can identify subsequences that are unique to a target        sequence, such as a mutant target sequence. Such an approach        would enable the use of siNA to target specifically the mutant        sequence and not effect the expression of the normal sequence.    -   3 In some instances the siNA subsequences are absent in one or        more sequences while present in the desired target sequence;        such would be the case if the siNA targets a gene with a        paralogous family member that is to remain untargeted. As in        case 2 above, a subsequence list of a particular length is        generated for each of the targets, and then the lists are        compared to find sequences that are present in the target gene        but are absent in the untargeted paralog.    -   4 The ranked siNA subsequences can be further analyzed and        ranked according to GC content. A preference can be given to        sites containing 30-70% GC, with a further preference to sites        containing 40-60% GC.    -   5 The ranked siNA subsequences can be further analyzed and        ranked according to self-folding and internal hairpins. Weaker        internal folds are preferred; strong hairpin structures are to        be avoided.    -   6 The ranked siNA subsequences can be further analyzed and        ranked according to whether they have runs of GGG or CCC in the        sequence. GGG (or even more Gs) in either strand can make        oligonucleotide synthesis problematic and can potentially        interfere with RNAi activity, so it is avoided whenever better        sequences are available. CCC is searched in the target strand        because that will place GGG in the antisense strand.    -   7 The ranked siNA subsequences can be further analyzed and        ranked according to whether they have the dinucleotide UU        (uridine dinucleotide) on the 3′-end of the sequence, and/or AA        on the 5′-end of the sequence (to yield 3′ UU on the antisense        sequence). These sequences allow one to design siNA molecules        with terminal TT thymidine dinucleotides.    -   8 Four or five target sites are chosen from the ranked list of        subsequences as described above. For example, in subsequences        having 23 nucleotides, the right 21 nucleotides of each chosen        23-mer subsequence are then designed and synthesized for the        upper (sense) strand of the siNA duplex, while the reverse        complement of the left 21 nucleotides of each chosen 23-mer        subsequence are then designed and synthesized for the lower        (antisense) strand of the siNA duplex. If terminal TT residues        are desired for the sequence (as described in paragraph 7), then        the two 3′ terminal nucleotides of both the sense and antisense        strands are replaced by TT prior to synthesizing the oligos.    -   9 The siNA molecules are screened in an in vitro, cell culture        or animal model system to identify the most active siNA molecule        or the most preferred target site within the target RNA        sequence.

In an alternate approach, a pool of siNA constructs specific to a targetsequence is used to screen for target sites in cells expressing targetRNA, such as human lung HeLa cells. A non-limiting example of such aspool is a pool comprising sequences having antisense sequencescomplementary to the target RNA sequence and sense sequencescomplementary to the antisense sequences. Cells (e.g., HeLa cells)expressing the target gene are transfected with the pool of siNAconstructs and cells that demonstrate a phenotype associated with genesilencing are sorted. The pool of siNA constructs can be chemicallymodified as described herein and synthesized, for example, in a highthroughput manner. The siNA from cells demonstrating a positivephenotypic change (e.g., decreased target mRNA levels or target proteinexpression), are identified, for example by positional analysis withinthe assay, and are used to determine the most suitable target site(s)within the target RNA sequence based upon the complementary sequence tothe corresponding siNA antisense strand identified in the assay.

Exemplary siNA Design

siNA target sites are chosen by analyzing sequences of the target RNAtarget and optionally prioritizing the target sites on the basis offolding (structure of any given sequence analyzed to determine siNAaccessibility to the target), by using a library of siNA molecules asdescribed, or alternately by using an in vitro siNA system as describedherein. siNA molecules were designed that could bind each target and areoptionally individually analyzed by computer folding to assess whetherthe siNA molecule can interact with the target sequence. Varying thelength of the siNA molecules can be chosen to optimize activity.Generally, a sufficient number of complementary nucleotide bases arechosen to bind to, or otherwise interact with, the target RNA, but thedegree of complementarity can be modulated to accommodate siNA duplexesor varying length or base composition. By using such methodologies, siNAmolecules can be designed to target sites within any known RNA sequence,for example those RNA sequences corresponding to the any genetranscript.

Chemically modified siNA constructs are designed to provide nucleasestability for systemic administration in vivo and/or improvedpharmacokinetic, localization, and delivery properties while preservingthe ability to mediate RNAi activity. Chemical modifications asdescribed herein are introduced synthetically using synthetic methodsdescribed herein and those generally known in the art. The syntheticsiNA constructs are then assayed for nuclease stability in serum and/orcellular/tissue extracts (e.g. liver extracts). The synthetic siNAconstructs are also tested in parallel for RNAi activity using anappropriate assay, such as a luciferase reporter assay as describedherein or another suitable assay that can quantity RNAi activity.Synthetic siNA constructs that possess both nuclease stability and RNAiactivity can be further modified and re-evaluated in stability andactivity assays. The chemical modifications of the stabilized activesiNA constructs can then be applied to any siNA sequence targeting anychosen RNA and used, for example, in target screening assays to picklead siNA compounds for therapeutic development.

RNAi In Vitro Assay to Assess siNA Activity

An in vitro assay that recapitulates RNAi in a cell free system is usedto evaluate siNA constructs specific to target RNA. The assay comprisesthe system described by Tuschl et al., 1999, Genes and Development, 13,3191-3197 and Zamore et al., 2000, Cell, 101, 25-33 adapted for use witha specific target RNA. A Drosophila extract derived from syncytialblastoderm is used to reconstitute RNAi activity in vitro. Target RNA isgenerated via in vitro transcription from an appropriate plasmid usingT7 RNA polymerase or via chemical synthesis as described herein. Senseand antisense siNA strands (for example 20 uM each) are annealed byincubation in buffer (such as 100 mM potassium acetate, 30 mM HEPES-KOH,pH 7.4, 2 mM magnesium acetate) for 1 min. at 90° C. followed by 1 hourat 37° C., then diluted in lysis buffer (for example 100 mM potassiumacetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate). Annealingcan be monitored by gel electrophoresis on an agarose gel in TBE bufferand stained with ethidium bromide. The Drosophila lysate is preparedusing zero to two hour old embryos from Oregon R flies collected onyeasted molasses agar that are dechorionated and lysed. The lysate iscentrifuged and the supernatant isolated. The assay comprises a reactionmixture containing 50% lysate [vol/vol], RNA (10-50 pM finalconcentration), and 10% [vol/vol] lysis buffer containing siNA (10 nMfinal concentration). The reaction mixture also contains 10 mM creatinephosphate, 10 ug.ml creatine phosphokinase, 100 um GTP, 100 uM UTP, 100uM CTP, 500 uM ATP, 5 mM DTT, 0.1 U/uL RNasin (Promega), and 100 uM ofeach amino acid. The final concentration of potassium acetate isadjusted to 100 mM. The reactions are pre-assembled on ice andpreincubated at 25° C. for 10 minutes before adding RNA, then incubatedat 25° C. for an additional 60 minutes. Reactions are quenched with 4volumes of 1.25× Passive Lysis Buffer (Promega). Target RNA cleavage isassayed by RT-PCR analysis or other methods known in the art and arecompared to control reactions in which siNA is omitted from thereaction.

Alternately, internally-labeled target RNA for the assay is prepared byin vitro transcription in the presence of [a-³²P] CTP, passed over a G50 Sephadex column by spin chromatography and used as target RNA withoutfurther purification. Optionally, target RNA is 5′-³²P-end labeled usingT4 oligonucleotide kinase enzyme. Assays are performed as describedabove and target RNA and the specific RNA cleavage products generated byRNAi are visualized on an autoradiograph of a gel. The percentage ofcleavage is determined by Phosphor Imager® quantitation of bandsrepresenting intact control RNA or RNA from control reactions withoutsiNA and the cleavage products generated by the assay.

In one embodiment, this assay is used to determine target sites in theRNA target for siNA mediated RNAi cleavage, wherein a plurality of siNAconstructs are screened for RNAi mediated cleavage of the RNA target,for example by analyzing the assay reaction by electrophoresis oflabeled target RNA, or by northern blotting, as well as by othermethodology well known in the art.

Specific hairless protein target sequences and the complementarysequences are provided as 19-mers in Table 1 following the Examples. Inthe table, the oligo number (first column on the left), e.g., 1, 2, 3,etc. matches the 1^(st) (5′) nucleotide in the reference sense cDNAsequence. Thus, Oligonucleotide 1 begins at nucleotide 1 in thereference hairless cDNA sequence, Oligonucleotide 2, begins atnucleotide 2 in the reference sequence, and so on. Thus, one skilled inthe art recognizes that the nucleotide position of each nucleotide ineach oligonucleotide in Table 1 is specified as if each nucleotide weremarked with the respective number.

The sequences shown in Table 1 are provided as DNA sequences, but oneskilled in the art understands that Table 1 also describes the matchingRNA sequence. One skilled in the art understands that the RNA sequencehas a U replacing each T shown in the DNA sequence. For example, forOligonucleotide 1 in Table 1, the DNA sequence is5′-TCTCCCGGGAGCCACTCCC-3′ (SEQ ID NO: 1), and the matching RNA sequenceis 5′-UCUCCCGGGAGCCACUCCC-3′ (SEQ ID NO: 11332).

While oligonucleotides are shown in Table 1 as 19-mers, this descriptionexpressly includes the additional 20-mer, 21-mer, 22-mer, 23-mer,24-mer, 25-mer, 26-mer, 27-mer, 28-mer, and 29-mer oligonucleotides asif they were included in the table. The sequence descriptions of those20-29-mers is provided by taking a starting 19-mer that has the same5′-nucleotide as the respective 20-29-mer, and adding the next 1, 2, 3,4, 5, 6, 7, 8, 9, or 10 3′-nucleotides from the subsequent 19-meroligonucleotides from the table. Thus, for example, the 19-mer sense RNAOligonucleotide 4 has the sequence: 5′-CCCGGGAGCCACUCCCAUG-3′ (SEQ IDNO:11333)

and the complementary 19-mer RNA described has the sequence5′-CAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO:11334)

Further, a 20-mer RNA that includes the Oligonucleotide 4 sequence isdescribed by the Oligo 4 sequence with the next nucleotide 3′, i.e., the3′-terminal G from Oligo 5. Thus, the 20-mer RNA described has thesequence 5′-CCCGGGAGCCACUCCCAUGG-3′ (SEQ ID NO:11335)

and the complementary 20-mer RNA described has the sequence5′-CCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO:11336)

Similarly, a 21-mer RNA that includes the Oligonucleotide 4 sequence isdescribed by the Oligo 4 sequence with the next two nucleotides 3′,i.e., the 3′-terminal GG from Oligo 6. Thus, the 21-mer RNA describedhas the sequence 5′-CCCGGGAGCCACUCCCAUGGG-3′ (SEQ ID NO:11337)

and the complementary 21-mer RNA described has the sequence5′-CCCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO:11338)

As the next oligonucleotide described, a 22-mer RNA that includes theOligonucleotide 4 sequence is described by the Oligo 4 sequence with thenext three nucleotides 3′, i.e., the 3′-terminal GGC from Oligo 7. Thus,the 22-mer RNA described has the sequence 5′-CCCGGGAGCCACUCCCAUGGGC-3′((SEQ ID NO:11339)

and the complementary 22-mer RNA described has the sequence5′-GCCCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO:11340)

A 23-mer RNA that includes the Oligonucleotide 4 sequence is describedby the Oligo 4 sequence with the next four nucleotides 3′, i.e., the3′-terminal GGCG from Oligo 8. Thus, the 23-mer RNA described has thesequence 5′-CCCGGGAGCCACUCCCAUGGGCG-3′ (SEQ ID NO:11341)

and the complementary 23-mer RNA described has the sequence5′-CGCCCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO:11342)

A 24-mer RNA that includes the Oligonucleotide 4 sequence is describedby the Oligo 4 sequence with the next five nucleotides 3′, i.e., the3′-terminal GGCGC from Oligo 9. Thus, the 24-mer RNA described has thesequence 5′-CCCGGGAGCCACUCCCAUGGGCGC-3′ (SEQ ID NO:11343)

and the complementary 24-mer RNA described has the sequence5′-GCGCCCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO:11344)

In similar fashion, a 25-mer that includes the Oligonucleotide 4sequence is described as 5′-CCCGGGAGCCACUCCCAUGGGCGCC-3′ (SEQ IDNO:11345)

and the complementary 25-mer RNA described has the sequence5′-GGCGCCCAUGGGAGUGGCUCCCGGG-3′. (SEQ ID NO:11346)

A 26-mer that includes the Oligonucleotide 4 sequence is described as5′-CCCGGGAGCCACUCCCAUGGGCGCCU-3′ (SEQ ID NO:11347)

and the complementary 26-mer RNA described has the sequence (SEQ IDNO:11348) 5′-AGGCGCCCAUGGGAGUGGCUCCCGGG-3′.

A 27-mer that includes the Oligonucleotide 4 sequence is described as(SEQ ID NO:11349) 5′-CCCGGGAGCCACUCCCAUGGGCGCCUC-3′

and the complementary 27-mer RNA described has the sequence (SEQ IDNO:11350) 5′-GAGGCGCCCAUGGGAGUGGCUCCCGGG-3′.

A 28-mer that includes the Oligonucleotide 4 sequence is described as(SEQ ID NO:11351) 5′-CCCGGGAGCCACUCCCAUGGGCGCCUCU-3′

and the complementary 28-mer RNA described has the sequence (SEQ IDNO:11352) 5′-AGAGGCGCCCAUGGGAGUGGCUCCCGGG-3′.

A 29-mer that includes the Oligonucleotide 4 sequence is described as(SEQ ID NO: 11353) 5′-CCCGGGAGCCACUCCCAUGGGCGCCUCUC-3′

and the complementary 29-mer RNA described has the sequence (SEQ ID NO:11354) 5′-GAGAGGCGCCCAUGGGAGUGGCUCCCGGG-3′.

Thus, Table 1 describes each of the 19-mers shown in Table 1 as DNA andRNA, and the corresponding 20-mers and longer.

In addition, the Table describes double stranded oligonucleotides withthe sense and antisense oligonucleotide strands hybridized, as well assuch double stranded oligonucleotides with one or both strands having a3′-overhang. Such an overhang consists of one or more 3′-terminalnucleotides of an oligonucleotide strand in a double stranded moleculethat are not hybridized with the complementary strand. In the presentcase, such overhang nucleotides often match the correspondingnucleotides from the target mRNA sequence, but can be different.

Table 1 also describes oligonucleotides that contain knownpolymorphisms. Those polymorphic sites are described in Table 2 alongwith the replacement nucleotide. Thus, Table 1 with Table 2 describesthe oligonucleotides with the alternate nucleotides at a polymorphicsite.

Chemical Modifications

As indicated above, for many applications it is advantageous to usechemically modified oligonucleotides rather than unmodified RNA for RNAi(e.g., siRNA). Such modification can dramatically increase the cellularand/or serum lifetime of the modified oligonucleotide compared to theunmodified form.

Description of such chemical modification is provided in McSwiggen etal., PCT/US03/05346, WO 03/070918. Thus, the introduction of chemicallymodified nucleotides into nucleic acid molecules assists in overcomingpotential limitations of in vivo stability and bioavailability inherentto native RNA molecules that are delivered exogenously. For example, theuse of chemically modified nucleic acid molecules can enable a lowerdose of a particular nucleic acid molecule for a given therapeuticeffect since chemically modified nucleic acid molecules tend to have alonger half-life in serum. Furthermore, certain chemical modificationscan improve the bioavailability of nucleic acid molecules by targetingparticular cells or tissues and/or improving cellular uptake of thenucleic acid molecule. Therefore, even if the activity of a chemicallymodified nucleic acid molecule is reduced as compared to a nativenucleic acid molecule, for example when compared to an all RNA nucleicacid molecule, the overall activity of the modified nucleic acidmolecule can be greater than the native molecule due to improvedstability and/or delivery of the molecule. Unlike native unmodifiedsiRNA, chemically modified siNA can also minimize the possibility ofactivating interferon activity in humans.

Thus, in some embodiments of the present invention, the nucleic acidmolecules that act as mediators of the RNA interference gene silencingresponse are chemically modified double stranded nucleic acid molecules,generally about 19-29 nucleotides in length. The most active siRNAmolecules are thought to have such duplexes with overhanging ends of 1-3nucleotides, for example 21 nucleotide duplexes with 19 base pairs and 2nucleotide 3-overhangs. These overhanging segments are readilyhydrolyzed by endonucleases in vivo. Studies have shown that replacingthe 3′-overhanging segments of a 21-mer siRNA duplex having 2 nucleotide3′ overhangs with deoxyribonucleotides does not have an adverse effecton RNAi activity. Replacing up to 4 nucleotides on each end of the siRNAwith deoxyribonucleotides has been reported to be well tolerated whereascomplete substitution with deoxyribonucleotides results in no RNAiactivity (Elbashir et al., 2001, EMBO J., 20, 6877). In addition,Elbashir et al. also report that full substitution of siRNA with2′-O-methyl nucleotides completely abolishes RNAi activity.

In some embodiments, the chemically modified siNA constructs havingspecificity for target nucleic acid molecules in a cell. Non-limitingexamples of such chemical modifications include without limitationphosphorothioate internucleotide linkages, 2′-O-methyl ribonucleotides,2′-deoxy-2′-fluoro ribonucleotides, “universal base” nucleotides,5-C-methyl nucleotides, and inverted deoxyabasic residue incorporation.These chemical modifications, when used in various siNA constructs, areshown to preserve RNAi activity in cells while at the same time,dramatically increasing the serum stability of these compounds.Furthermore, contrary to the data published by Parrish et al., supra,applicant demonstrates that multiple (greater than one) phosphorothioatesubstitutions are well-tolerated and confer substantial increases inserum stability for modified siNA constructs.

In one embodiment, a siNA molecule of the invention comprises modifiednucleotides while maintaining the ability to mediate RNAi. The modifiednucleotides can be used to improve in vitro or in vivo characteristicssuch as stability, activity, and/or bioavailability. For example, a siNAmolecule of the invention can comprise modified nucleotides as apercentage of the total number of nucleotides present in the siNAmolecule. As such, a siNA molecule of the invention can generallycomprise modified nucleotides at between 5 and 100% of the nucleotidepositions (e.g., 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the nucleotidepositions). The actual percentage of modified nucleotides present in agiven siNA molecule will depend on the total number of nucleotidespresent in the siNA. If the siNA molecule is single stranded, thepercent modification can be based upon the total number of nucleotidespresent in the single stranded siNA molecules. Likewise, if the siNAmolecule is double stranded, the percent modification can be based uponthe total number of nucleotides present in the sense strand, antisensestrand, or both the sense and antisense strands. In addition, the actualpercentage of modified nucleotides present in a given siNA molecule canalso depend on the total number of purine and pyrimidine nucleotidespresent in the siNA, for example wherein all pyrimidine nucleotidesand/or all purine nucleotides present in the siNA molecule are modified.

In a non-limiting example, the introduction of chemically-modifiednucleotides into nucleic acid molecules will provide a powerful tool inovercoming potential limitations of in vivo stability andbioavailability inherent to native RNA molecules that are deliveredexogenously. For example, the use of chemically-modified nucleic acidmolecules can enable a lower dose of a particular nucleic acid moleculefor a given therapeutic effect since chemically-modified nucleic acidmolecules tend to have a longer half-life in serum. Furthermore, certainchemical modifications can improve the bioavailability of nucleic acidmolecules by targeting particular cells or tissues and/or improvingcellular uptake of the nucleic acid molecule. Therefore, even if theactivity of a chemically-modified nucleic acid molecule is reduced ascompared to a native nucleic acid molecule, for example when compared toan all-RNA nucleic acid molecule, the overall activity of the modifiednucleic acid molecule can be greater than that of the native moleculedue to improved stability and/or delivery of the molecule. Unlike nativeunmodified siNA, chemically-modified siNA can also minimize thepossibility of activating interferon activity in humans.

The antisense region of a siNA molecule of the invention can comprise aphosphorothioate internucleotide linkage at the 3′-end of said antisenseregion. The antisense region can comprise between about one and aboutfive phosphorothioate internucleotide linkages at the 5′-end of saidantisense region. The 3′-terminal nucleotide overhangs of a siNAmolecule of the invention can comprise ribonucleotides ordeoxyribonucleotides that are chemically-modified at a nucleic acidsugar, base, or backbone. The 3′-terminal nucleotide overhangs cancomprise one or more universal base ribonucleotides. The 3′-terminalnucleotide overhangs can comprise one or more acyclic nucleotides.

In certain embodiments, the chemically-modified short interferingnucleic acid (siNA) molecule capable of mediating RNA interference(RNAi) inside a cell or reconstituted in vitro system, includes one ormore chemically modified nucleotides (e.g., about 1, 2, 3, 4, 5, 6, 7,8, 9, 10, or more) comprising a backbone modified internucleotidelinkage having Formula I:

wherein each R1 and R2 is independently any nucleotide, non-nucleotide,or oligonucleotide which can be naturally-occurring orchemically-modified, each X and Y is independently O, S, N, alkyl, orsubstituted alkyl, each Z and W is independently O, S, N, alkyl,substituted alkyl, O-alkyl, S-alkyl, alkaryl, or aralkyl, and wherein W,X, Y, and Z are optionally not all O.

The chemically-modified internucleotide linkages having Formula I, forexample wherein any Z, W, X, and/or Y independently comprises a sulphuratom, can be present in one or both oligonucleotide strands of the siNAduplex, for example in the sense strand, the antisense strand, or bothstrands. The siNA molecules of the invention can comprise one or more(e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) chemically-modifiedinternucleotide linkages having Formula I at the 3′-end, the 5′-end, orboth of the 3′ and 5′-ends of the sense strand, the antisense strand, orboth strands. For example, an exemplary siNA molecule of the inventioncan comprise between about 1 and about 5 or more (e.g., about 1, 2, 3,4, 5, or more) chemically-modified internucleotide linkages havingFormula I at the 5′-end of the sense strand, the antisense strand, orboth strands. In another non-limiting example, an exemplary siNAmolecule of the invention can comprise one or more (e.g., about 1, 2, 3,4, 5, 6, 7, 8, 9, 10, or more) pyrimidine nucleotides withchemically-modified internucleotide linkages having Formula I in thesense strand, the antisense strand, or both strands. In yet anothernon-limiting example, an exemplary siNA molecule of the invention cancomprise one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, ormore) purine nucleotides with chemically-modified internucleotidelinkages having Formula I in the sense strand, the antisense strand, orboth strands. In another embodiment, a siNA molecule of the inventionhaving internucleotide linkage(s) of Formula I also comprises achemically-modified nucleotide or non-nucleotide having any of FormulaeI-VII.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule capable of mediating RNAinterference (RNAi) inside a cell or reconstituted in vitro system,wherein the chemical modification comprises one or more (e.g., about 1,2, 3, 4, 5, 6, 7, 8, 9, 10, or more) nucleotides or non-nucleotideshaving Formula II:

wherein each R3, R4, R5, R6, R7, R8, R10, R1 and R12 is independently H,OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3,OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl,SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH,S-alkyl-SH, alkyl-5-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2,aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid,O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino,polyalklylamino, substituted silyl, or group having Formula I; R9 is O,S, CH2, S═O, CHF, or CF2, and B is a nucleosidic base such as adenine,guanine, uracil, cytosine, thymine, 2-aminoadenosine, 5-methylcytosine,2,6-diaminopurine, or any other non-naturally occurring base that can becomplementary or non-complementary to target RNA or a non-nucleosidicbase such as phenyl, naphthyl, 3-nitropyrrole, 5-nitroindole,nebularine, pyridone, pyridinone, or any other non-naturally occurringuniversal base that can be complementary or non-complementary to targetRNA.

The chemically-modified nucleotide or non-nucleotide of Formula II canbe present in one or both oligonucleotide strands of the siNA duplex,for example in the sense strand, the antisense strand, or both strands.The siNA molecules of the invention can comprise one or morechemically-modified nucleotide or non-nucleotide of Formula II at the3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense strand,the antisense strand, or both strands. For example, an exemplary siNAmolecule of the invention can comprise between about 1 and about 5 ormore (e.g., about 1, 2, 3, 4, 5, or more) chemically-modifiednucleotides or non-nucleotides of Formula II at the 5′-end of the sensestrand, the antisense strand, or both strands. In anther non-limitingexample, an exemplary siNA molecule of the invention can comprisebetween about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more)chemically-modified nucleotides or non-nucleotides of Formula II at the3′-end of the sense strand, the antisense strand, or both strands.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule capable of mediating RNAinterference (RNAi) inside a cell or reconstituted in vitro system,wherein the chemical modification comprises one or more (e.g., about 1,2, 3, 4, 5, 6, 7, 8, 9, 10, or more) nucleotides or non-nucleotideshaving Formula III:

wherein each R3, R4, R5, R6, R7, R8, R10, R11 and R12 is independentlyH, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF3,OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl,SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH, O-alkyl-SH, S-alkyl-OH,S-alkyl-SH, alkyl-5-alkyl, alkyl-O-alkyl, ONO2, NO2, N3, NH2,aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl, O-aminoacid,O-aminoacyl, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino,polyalklylamino, substituted silyl, or group having Formula I; R9 is O,S, CH2, S═O, CHF, or CF2, and B is a nucleosidic base such as adenine,guanine, uracil, cytosine, thymine, 2-aminoadenosine, 5-methylcytosine,2,6-diaminopurine, or any other non-naturally occurring base that can beemployed to be complementary or non-complementary to target RNA or anon-nucleosidic base such as phenyl, naphthyl, 3-nitropyrrole,5-nitroindole, nebularine, pyridone, pyridinone, or any othernon-naturally occurring universal base that can be complementary ornon-complementary to target RNA.

The chemically-modified nucleotide or non-nucleotide of Formula III canbe present in one or both oligonucleotide strands of the siNA duplex,for example in the sense strand, the antisense strand, or both strands.The siNA molecules of the invention can comprise one or morechemically-modified nucleotide or non-nucleotide of Formula III at the3′-end, the 5′-end, or both of the 3′ and 5′-ends of the sense strand,the antisense strand, or both strands. For example, an exemplary siNAmolecule of the invention can comprise between about 1 and about 5 ormore (e.g., about 1, 2, 3, 4, 5, or more) chemically-modifiednucleotide(s) or non-nucleotide(s) of Formula III at the 5′-end of thesense strand, the antisense strand, or both strands. In anthernon-limiting example, an exemplary siNA molecule of the invention cancomprise between about 1 and about 5 or more (e.g., about 1, 2, 3, 4, 5,or more) chemically-modified nucleotide or non-nucleotide of Formula IIIat the 3′-end of the sense strand, the antisense strand, or bothstrands.

In another embodiment, a siNA molecule of the invention comprises anucleotide having Formula II or III, wherein the nucleotide havingFormula II or III is in an inverted configuration. For example, thenucleotide having Formula II or III is connected to the siNA constructin a 3′-3′,3′-2′,2′-3′, or 5′-5′ configuration, such as at the 3′-end,the 5′-end, or both of the 3′ and 5′-ends of one or both siNA strands.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule capable of mediating RNAinterference (RNAi) inside a cell or reconstituted in vitro system,wherein the chemical modification comprises a 5′-terminal phosphategroup having Formula IV:

wherein each X and Y is independently O, S, N, alkyl, substituted alkyl,or alkylhalo; wherein each Z and W is independently O, S, N, alkyl,substituted alkyl, O-alkyl, S-alkyl, alkaryl, aralkyl, or alkylhalo; andwherein W, X, Y and Z are not all O.

In one embodiment, the invention features a siNA molecule having a5′-terminal phosphate group having Formula IV on thetarget-complementary strand, for example a strand complementary to atarget RNA, wherein the siNA molecule comprises an all RNA siNAmolecule. In another embodiment, the invention features a siNA moleculehaving a 5′-terminal phosphate group having Formula IV on thetarget-complementary strand wherein the siNA molecule also comprisesabout 1-3 (e.g., about 1, 2, or 3) nucleotide 3′-terminal nucleotideoverhangs having between about 1 and about 4 (e.g., about 1, 2, 3, or 4)deoxyribonucleotides on the 3′-end of one or both strands. In anotherembodiment, a 5′-terminal phosphate group having Formula IV is presenton the target-complementary strand of a siNA molecule of the invention,for example a siNA molecule having chemical modifications having any ofFormulae I-VII.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule capable of mediating RNAinterference (RNAi) inside a cell or reconstituted in vitro system,wherein the chemical modification comprises one or more phosphorothioateinternucleotide linkages. For example, in a non-limiting example, theinvention features a chemically-modified short interfering nucleic acid(siNA) having about 1, 2, 3, 4, 5, 6, 7, 8 or more phosphorothioateinternucleotide linkages in one siNA strand. In yet another embodiment,the invention features a chemically-modified short interfering nucleicacid (siNA) individually having about 1, 2, 3, 4, 5, 6, 7, 8 or morephosphorothioate internucleotide linkages in both siNA strands. Thephosphorothioate internucleotide linkages can be present in one or botholigonucleotide strands of the siNA duplex, for example in the sensestrand, the antisense strand, or both strands. The siNA molecules of theinvention can comprise one or more phosphorothioate internucleotidelinkages at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends ofthe sense strand, the antisense strand, or both strands. For example, anexemplary siNA molecule of the invention can comprise between about 1and about 5 or more (e.g., about 1, 2, 3, 4, 5, or more) consecutivephosphorothioate internucleotide linkages at the 5′-end of the sensestrand, the antisense strand, or both strands. In another non-limitingexample, an exemplary siNA molecule of the invention can comprise one ormore (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) pyrimidinephosphorothioate internucleotide linkages in the sense strand, theantisense strand, or both strands. In yet another non-limiting example,an exemplary siNA molecule of the invention can comprise one or more(e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) purinephosphorothioate internucleotide linkages in the sense strand, theantisense strand, or both strands.

In one embodiment, the invention features a siNA molecule, wherein thesense strand comprises one or more, for example about 1, 2, 3, 4, 5, 6,7, 8, 9, 10, or more phosphorothioate internucleotide linkages, and/orone or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more)2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g.,about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modifiednucleotides, and optionally a terminal cap molecule at the 3′ end, the5′-end, or both of the 3′- and 5′-ends of the sense strand; and whereinthe antisense strand comprises any of between 1 and 10 or more,specifically about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or morephosphorothioate internucleotide linkages, and/or one or more (e.g.,about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl,2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7,8, 9, 10 or more) universal base modified nucleotides, and optionally aterminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and5′-ends of the antisense strand. In another embodiment, one or more, forexample about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, pyrimidinenucleotides of the sense and/or antisense siNA strand arechemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoronucleotides, with or without one or more, for example about 1, 2, 3, 4,5, 6, 7, 8, 9, 10, or more, phosphorothioate internucleotide linkagesand/or a terminal cap molecule at the 3′-end, the 5′-end, or both of the3′- and 5′-ends, being present in the same or different strand.

In another embodiment, the invention features a siNA molecule, whereinthe sense strand comprises between about 1 and about 5, specificallyabout 1, 2, 3, 4, or 5 phosphorothioate internucleotide linkages, and/orone or more (e.g., about 1, 2, 3, 4, 5, or more) 2′-deoxy, 2′-O-methyl,2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, ormore) universal base modified nucleotides, and optionally a terminal capmolecule at the 3-end, the 5′-end, or both of the 3′- and 5′-ends of thesense strand; and wherein the antisense strand comprises any of betweenabout 1 and about 5 or more, specifically about 1, 2, 3, 4, 5, or morephosphorothioate internucleotide linkages, and/or one or more (e.g.,about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl,2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7,8, 9, 10 or more) universal base modified nucleotides, and optionally aterminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and5′-ends of the antisense strand. In another embodiment, one or more, forexample about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, pyrimidinenucleotides of the sense and/or antisense siNA strand arechemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoronucleotides, with or without between about 1 and about 5 or more, forexample about 1, 2, 3, 4, 5, or more phosphorothioate internucleotidelinkages and/or a terminal cap molecule at the 3′-end, the 5′-end, orboth of the 3′- and 5′-ends, being present in the same or differentstrand.

In one embodiment, the invention features a siNA molecule, wherein theantisense strand comprises one or more, for example about 1, 2, 3, 4, 5,6, 7, 8, 9, 10, or more phosphorothioate internucleotide linkages,and/or between one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 ormore) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more(e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) universal basemodified nucleotides, and optionally a terminal cap molecule at the3′-end, the 5′-end, or both of the 3′- and 5′-ends of the sense strand;and wherein the antisense strand comprises any of between about 1 andabout 10, specifically about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or morephosphorothioate internucleotide linkages, and/or one or more (e.g.,about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl,2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7,8, 9, 10 or more) universal base modified nucleotides, and optionally aterminal cap molecule at the 3′-end, the 5′-end, or both of the 3′- and5′-ends of the antisense strand. In another embodiment, one or more, forexample about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more pyrimidinenucleotides of the sense and/or antisense siNA strand arechemically-modified with 2′-deoxy, 2′-O-methyl and/or 2′-deoxy-2′-fluoronucleotides, with or without one or more, for example about 1, 2, 3, 4,5, 6, 7, 8, 9, 10 or more phosphorothioate internucleotide linkagesand/or a terminal cap molecule at the 3′-end, the 5′-end, or both of the3′ and 5′-ends, being present in the same or different strand.

In another embodiment, the invention features a siNA molecule, whereinthe antisense strand comprises between about 1 and about 5 or more,specifically about 1, 2, 3, 4, 5 or more phosphorothioateinternucleotide linkages, and/or one or more (e.g., about 1, 2, 3, 4, 5,6, 7, 8, 9, 10 or more) 2′-deoxy, 2′-O-methyl, 2′-deoxy-2′-fluoro,and/or one or more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more)universal base modified nucleotides, and optionally a terminal capmolecule at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends ofthe sense strand; and wherein the antisense strand comprises any ofbetween about 1 and about 5 or more, specifically about 1, 2, 3, 4, 5 ormore phosphorothioate internucleotide linkages, and/or one or more(e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) 2′-deoxy,2′-O-methyl, 2′-deoxy-2′-fluoro, and/or one or more (e.g., about 1, 2,3, 4, 5, 6, 7, 8, 9, 10 or more) universal base modified nucleotides,and optionally a terminal cap molecule at the 3′-end, the 5′-end, orboth of the 3′- and 5′-ends of the antisense strand. In anotherembodiment, one or more, for example about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10or more pyrimidine nucleotides of the sense and/or antisense siNA strandare chemically-modified with 2′-deoxy, 2′-O-methyl and/or2′-deoxy-2′-fluoro nucleotides, with or without between about 1 andabout 5, for example about 1, 2, 3, 4, 5 or more phosphorothioateinternucleotide linkages and/or a terminal cap molecule at the 3′-end,the 5′-end, or both of the 3′- and 5′-ends, being present in the same ordifferent strand.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule having between about 1 andabout 5, specifically about 1, 2, 3, 4, 5 or more phosphorothioateinternucleotide linkages in each strand of the siNA molecule.

In another embodiment, the invention features a siNA molecule comprising2′-5′ internucleotide linkages. The 2′-5′ internucleotide linkage(s) canbe at the 3′-end, the 5′-end, or both of the 3′- and 5′-ends of one orboth siNA sequence strands.

In addition, the 2′-5′ internucleotide linkage(s) can be present atvarious other positions within one or both siNA sequence strands, forexample, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more including everyinternucleotide linkage of a pyrimidine nucleotide in one or bothstrands of the siNA molecule can comprise a 2′-5′ internucleotidelinkage, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more including everyinternucleotide linkage of a purine nucleotide in one or both strands ofthe siNA molecule can comprise a 2′-5′ internucleotide linkage.

In another embodiment, a chemically-modified siNA molecule of theinvention comprises a duplex having two strands, one or both of whichcan be chemically-modified, wherein each strand is between about 18 andabout 27 (e.g., about 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27)nucleotides in length, wherein the duplex has between about 18 and about23 (e.g., about 18, 19, 20, 21, 22, or 23) base pairs, and wherein thechemical modification comprises a structure having any of FormulaeI-VII. For example, an exemplary chemically-modified siNA molecule ofthe invention comprises a duplex having two strands, one or both ofwhich can be chemically-modified with a chemical modification having anyof Formulae I-VII or any combination thereof, wherein each strandconsists of about 21 nucleotides, each having a 2-nucleotide 3′-terminalnucleotide overhang, and wherein the duplex has about 19 base pairs. Inanother embodiment, a siNA molecule of the invention comprises a singlestranded hairpin structure, wherein the siNA is between about 36 andabout 70 (e.g., about 36, 40, 45, 50, 55, 60, 65, or 70) nucleotides inlength having between about 18 and about 23 (e.g., about 18, 19, 20, 21,22, or 23) base pairs, and wherein the siNA can include a chemicalmodification comprising a structure having any of Formulae I-VII or anycombination thereof. For example, an exemplary chemically-modified siNAmolecule of the invention comprises a linear oligonucleotide havingbetween about 42 and about 50 (e.g., about 42, 43, 44, 45, 46, 47, 48,49, or 50) nucleotides that is chemically-modified with a chemicalmodification having any of Formulae I-VII or any combination thereof,wherein the linear oligonucleotide forms a hairpin structure havingabout 19 base pairs and a 2-nucleotide 3′-terminal nucleotide overhang.In another embodiment, a linear hairpin siNA molecule of the inventioncontains a stem loop motif, wherein the loop portion of the siNAmolecule is biodegradable. For example, a linear hairpin siNA moleculeof the invention is designed such that degradation of the loop portionof the siNA molecule in vivo can generate a double-stranded siNAmolecule with 3′-terminal overhangs, such as 3′-terminal nucleotideoverhangs comprising about 2 nucleotides.

In another embodiment, a siNA molecule of the invention comprises acircular nucleic acid molecule, wherein the siNA is between about 38 andabout 70 (e.g., about 38, 40, 45, 50, 55, 60, 65, or 70) nucleotides inlength having between about 18 and about 23 (e.g., about 18, 19, 20, 21,22, or 23) base pairs, and wherein the siNA can include a chemicalmodification, which comprises a structure having any of Formulae I-VIIor any combination thereof. For example, an exemplarychemically-modified siNA molecule of the invention comprises a circularoligonucleotide having between about 42 and about 50 (e.g., about 42,43, 44, 45, 46, 47, 48, 49, or 50) nucleotides that ischemically-modified with a chemical modification having any of FormulaeI-VII or any combination thereof, wherein the circular oligonucleotideforms a dumbbell shaped structure having about 19 base pairs and 2loops.

In another embodiment, a circular siNA molecule of the inventioncontains two loop motifs, wherein one or both loop portions of the siNAmolecule is biodegradable. For example, a circular siNA molecule of theinvention is designed such that degradation of the loop portions of thesiNA molecule in vivo can generate a double-stranded siNA molecule with3′-terminal overhangs, such as 3′-terminal nucleotide overhangscomprising about 2 nucleotides.

In one embodiment, a siNA molecule of the invention comprises at leastone (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) abasic moiety,for example a compound having Formula V:

wherein each R3, R4, R5, R6, R7, R8, R10, R11, R12, and R13 isindependently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F,Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl,S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH,O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-5-alkyl, alkyl-O-alkyl, ONO2,NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl,O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl,aminoalkylamino, polyalklylamino, substituted silyl, or group havingFormula I; R9 is O, S, CH2, S═O, CHF, or CF2.

In one embodiment, a siNA molecule of the invention comprises at leastone (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) inverted abasicmoiety, for example a compound having Formula VI:

wherein each R3, R4, R5, R6, R7, R8, R10, R11, R12, and R13 isindependently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F,Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl,S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH,O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-5-alkyl, alkyl-O-alkyl, ONO2,NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl,O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl,aminoalkylamino, polyalklylamino, substituted silyl, or group havingFormula I; R9 is O, S, CH2, S═O, CHF, or CF2, and either R2, R3, R8 orR13 serve as points of attachment to the siNA molecule of the invention.

In another embodiment, a siNA molecule of the invention comprises atleast one (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more)substituted polyalkyl moieties, for example a compound having FormulaVII:

wherein each n is independently an integer from 1 to 12, each R1, R2 andR3 is independently H, OH, alkyl, substituted alkyl, alkaryl or aralkyl,F, Cl, Br, CN, CF3, OCF3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl,S-alkenyl, N-alkenyl, SO-alkyl, alkyl-OSH, alkyl-OH, O-alkyl-OH,O-alkyl-SH, S-alkyl-OH, S-alkyl-SH, alkyl-5-alkyl, alkyl-O-alkyl, ONO2,NO2, N3, NH2, aminoalkyl, aminoacid, aminoacyl, ONH2, O-aminoalkyl,O-aminoacid, O-aminoacyl, heterocycloalkyl, heterocycloalkaryl,aminoalkylamino, polyalklylamino, substituted silyl, or a group havingFormula I, and R1, R2 or R3 serves as points of attachment to the siNAmolecule of the invention.

In another embodiment, the invention features a compound having FormulaVII, wherein R1 and R2 are hydroxyl (OH) groups, n=1, and R3 comprises Oand is the point of attachment to the 3′-end, the 5′-end, or both of the3′ and 5′-ends of one or both strands of a double-stranded siNA moleculeof the invention or to a single-stranded siNA molecule of the invention.This modification is referred to herein as “glyceryl”.

In another embodiment, a moiety having any of Formula V, VI or VII ofthe invention is at the 3′-end, the 5′-end, or both of the 3′ and5′-ends of a siNA molecule of the invention. For example, a moietyhaving Formula V, VI or VII can be present at the 3′-end, the 5′-end, orboth of the 3′ and 5′-ends of the antisense strand, the sense strand, orboth antisense and sense strands of the siNA molecule. In addition, amoiety having Formula VII can be present at the 3′-end or the 5′-end ofa hairpin siNA molecule as described herein.

In another embodiment, a siNA molecule of the invention comprises anabasic residue having Formula V or VI, wherein the abasic residue havingFormula VI or VI is connected to the siNA construct in a3′-3′,3′-2′,2′-3′, or 5′-5′ configuration, such as at the 3′-end, the5′-end, or both of the 3′ and 5′-ends of one or both siNA strands.

In one embodiment, a siNA molecule of the invention comprises one ormore (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) locked nucleicacid (LNA) nucleotides, for example at the 5′-end, the 3′-end, both ofthe 5′ and 3′-ends, or any combination thereof, of the siNA molecule.

In another embodiment, a siNA molecule of the invention comprises one ormore (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) acyclicnucleotides, for example at the 5′-end, the 3′-end, both of the 5′ and3′-ends, or any combination thereof, of the siNA molecule.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule of the invention, wherein thechemically-modified siNA comprises a sense region, where any (e.g., oneor more or all) pyrimidine nucleotides present in the sense region are2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidinenucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternatelya plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidinenucleotides), and where any (e.g., one or more or all) purinenucleotides present in the sense region are 2′-deoxy purine nucleotides(e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides oralternately a plurality of purine nucleotides are 2′-deoxy purinenucleotides).

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule of the invention, wherein thechemically-modified siNA comprises a sense region, where any (e.g., oneor more or all) pyrimidine nucleotides present in the sense region are2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidinenucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternatelya plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidinenucleotides), and where any (e.g., one or more or all) purinenucleotides present in the sense region are 2′-deoxy purine nucleotides(e.g., wherein all purine nucleotides are 2′-deoxy purine nucleotides oralternately a plurality of purine nucleotides are 2′-deoxy purinenucleotides), wherein any nucleotides comprising a 3′-terminalnucleotide overhang that are present in said sense region are 2′-deoxynucleotides.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule of the invention, wherein thechemically-modified siNA comprises an antisense region, where any (e.g.,one or more or all) pyrimidine nucleotides present in the antisenseregion are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein allpyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides oralternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides), and wherein any (e.g., one or more or all)purine nucleotides present in the antisense region are 2′-O-methylpurine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methylpurine nucleotides or alternately a plurality of purine nucleotides are2′-O-methyl purine nucleotides).

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule of the invention, wherein thechemically-modified siNA comprises an antisense region, where any (e.g.,one or more or all) pyrimidine nucleotides present in the antisenseregion are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein allpyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides oralternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides), and wherein any (e.g., one or more or all)purine nucleotides present in the antisense region are 2′-O-methylpurine nucleotides (e.g., wherein all purine nucleotides are 2′-O-methylpurine nucleotides or alternately a plurality of purine nucleotides are2′-O-methyl purine nucleotides), wherein any nucleotides comprising a3′-terminal nucleotide overhang that are present in said antisenseregion are 2′-deoxy nucleotides.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule of the invention, wherein thechemically-modified siNA comprises an antisense region, where any (e.g.,one or more or all) pyrimidine nucleotides present in the antisenseregion are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein allpyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides oralternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides), and where any (e.g., one or more or all) purinenucleotides present in the antisense region are 2′-deoxy purinenucleotides (e.g., wherein all purine nucleotides are 2′-deoxy purinenucleotides or alternately a plurality of purine nucleotides are2′-deoxy purine nucleotides).

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule of the invention capable ofmediating RNA interference (RNAi) inside a cell or reconstituted invitro system, wherein the chemically-modified siNA comprises a senseregion, where one or more pyrimidine nucleotides present in the senseregion are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein allpyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides oralternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides), and where one or more purine nucleotidespresent in the sense region are 2′-deoxy purine nucleotides (e.g.,wherein all purine nucleotides are 2′-deoxy purine nucleotides oralternately a plurality of purine nucleotides are 2′-deoxy purinenucleotides), and inverted deoxy abasic modifications that areoptionally present at the 3′-end, the 5′-end, or both of the 3′ and5′-ends of the sense region, the sense region optionally furthercomprising a 3′-terminal overhang having between about 1 and about 4(e.g, about 1, 2, 3, or 4) 2′-deoxyribonucleotides; and wherein thechemically-modified short interfering nucleic acid molecule comprises anantisense region, where one or more pyrimidine nucleotides present inthe antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides(e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides or alternately a plurality of pyrimidinenucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and whereinone or more purine nucleotides present in the antisense region are2′-O-methyl purine nucleotides (e.g., wherein all purine nucleotides are2′-O-methyl purine nucleotides or alternately a plurality of purinenucleotides are 2′-O-methyl purine nucleotides), and a terminal capmodification, such as any modification described herein, that isoptionally present at the 3′-end, the 5′-end, or both of the 3′ and5′-ends of the antisense sequence, the antisense region optionallyfurther comprising a 3′-terminal nucleotide overhang having betweenabout 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxynucleotides,wherein the overhang nucleotides can further comprise one or more (e.g.,1, 2, 3, or 4) phosphorothioate internucleotide linkages.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule of the invention capable ofmediating RNA interference (RNAi) inside a cell or reconstituted invitro system, wherein the siNA comprises a sense region, where one ormore pyrimidine nucleotides present in the sense region are2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein all pyrimidinenucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides or alternatelya plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidinenucleotides), and where one or more purine nucleotides present in thesense region are purine ribonucleotides (e.g., wherein all purinenucleotides are purine ribonucleotides or alternately a plurality ofpurine nucleotides are purine ribonucleotides), and inverted deoxyabasic modifications that are optionally present at the 3′-end, the5′-end, or both of the 3′ and 5′-ends of the sense region, the senseregion optionally further comprising a 3′-terminal overhang havingbetween about 1 and about 4 (e.g, about 1, 2, 3, or 4)2′-deoxyribonucleotides; and wherein the siNA comprises an antisenseregion, where one or more pyrimidine nucleotides present in theantisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g.,wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidinenucleotides or alternately a plurality of pyrimidine nucleotides are2′-deoxy-2′-fluoro pyrimidine nucleotides), and wherein any purinenucleotides present in the antisense region are 2′-O-methyl purinenucleotides (e.g., wherein all purine nucleotides are 2′-O-methyl purinenucleotides or alternately a plurality of purine nucleotides are2′-O-methyl purine nucleotides), and a terminal cap modification, suchas any modification described herein, that is optionally present at the3′-end, the 5′-end, or both of the 3′ and 5′-ends of the antisensesequence, the antisense region optionally further comprising a3′-terminal nucleotide overhang having between about 1 and about 4 (e.g,about 1, 2, 3, or 4) 2′-deoxynucleotides, wherein the overhangnucleotides can further comprise one or more (e.g., 1, 2, 3, or 4)phosphorothioate internucleotide linkages.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid (siNA) molecule of the invention capable ofmediating RNA interference (RNAi) inside a cell or reconstituted invitro system, wherein the chemically-modified siNA comprises a senseregion, where one or more pyrimidine nucleotides present in the senseregion are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein allpyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides oralternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides), and for example where one or more purinenucleotides present in the sense region are selected from the groupconsisting of 2′-deoxy nucleotides, locked nucleic acid (LNA)nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and2′-O-methyl nucleotides (e.g., wherein all purine nucleotides areselected from the group consisting of 2′-deoxy nucleotides, lockednucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides,4′-thionucleotides, and 2′-O-methyl nucleotides or alternately aplurality of purine nucleotides are selected from the group consistingof 2′-deoxy nucleotides, locked nucleic acid (LNA) nucleotides,2′-methoxyethyl nucleotides, 4′-thionucleotides, and 2′-O-methylnucleotides), and wherein inverted deoxy abasic modifications areoptionally present at the 3′-end, the 5′-end, or both of the 3′ and5′-ends of the sense region, the sense region optionally furthercomprising a 3′-terminal overhang having between about 1 and about 4(e.g, about 1, 2, 3, or 4) 2′-deoxyribonucleotides; and wherein thechemically-modified short interfering nucleic acid molecule comprises anantisense region, where one or more pyrimidine nucleotides present inthe antisense region are 2′-deoxy-2′-fluoro pyrimidine nucleotides(e.g., wherein all pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides or alternately a plurality of pyrimidinenucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides), and whereinone or more purine nucleotides present in the antisense region areselected from the group consisting of 2′-deoxy nucleotides, lockednucleic acid (LNA) nucleotides, 2′-methoxyethyl nucleotides,4′-thionucleotides, and 2′-O-methyl nucleotides (e.g., wherein allpurine nucleotides are selected from the group consisting of 2′-deoxynucleotides, locked nucleic acid (LNA) nucleotides, 2′-methoxyethylnucleotides, 4′-thionucleotides, and 2′-O-methyl nucleotides oralternately a plurality of purine nucleotides are selected from thegroup consisting of 2′-deoxy nucleotides, locked nucleic acid (LNA)nucleotides, 2′-methoxyethyl nucleotides, 4′-thionucleotides, and2′-O-methyl nucleotides), and a terminal cap modification, that isoptionally present at the 3′-end, the 5′-end, or both of the 3′ and5′-ends of the antisense sequence, the antisense region optionallyfurther comprising a 3′-terminal nucleotide overhang having betweenabout 1 and about 4 (e.g, about 1, 2, 3, or 4) 2′-deoxynucleotides,wherein the overhang nucleotides can further comprise one or more (e.g.,1, 2, 3, or 4) phosphorothioate internucleotide linkages.

In another embodiment, any modified nucleotides present in the siNAmolecules of the invention, preferably in the antisense strand of thesiNA molecules of the invention, comprise modified nucleotides havingproperties or characteristics similar to naturally occurringribonucleotides. For example, the invention features siNA moleculesincluding modified nucleotides having a Northern conformation (e.g.,Northern pseudorotation cycle, see for example Saenger, Principles ofNucleic Acid Structure, Springer-Verlag ed., 1984). As such, chemicallymodified nucleotides present in the siNA molecules of the invention,preferably in the antisense strand of the siNA molecules of theinvention, are preferably resistant to nuclease degradation while at thesame time maintaining the capacity to mediate RNAi. Non-limitingexamples of nucleotides having a northern configuration include lockednucleic acid (LNA) nucleotides (e.g.,2′-O,4′-C-methylene-(D-ribofuranosyl) nucleotides); 2′-methoxyethoxy(MOE) nucleotides; 2′-deoxy-2′-fluoro nucleotides, 2′-deoxy-2′-chloronucleotides, 2′-azido nucleotides, and 2′-O-methyl nucleotides.

In one embodiment, the invention features a chemically-modified shortinterfering nucleic acid molecule (siNA) capable of mediating RNAinterference (RNAi) inside a cell or reconstituted in vitro system,wherein the chemical modification comprises one or more conjugatescovalently attached to the chemically-modified siNA molecule. In anotherembodiment, the conjugate is covalently attached to thechemically-modified siNA molecule via a biodegradable linker. In oneembodiment, the conjugate molecule is attached at the 3′-end of eitherthe sense strand, the antisense strand, or both strands of thechemically-modified siNA molecule. In another embodiment, the conjugatemolecule is attached at the 5′-end of either the sense strand, theantisense strand, or both strands of the chemically-modified siNAmolecule. In yet another embodiment, the conjugate molecule is attachedboth the 3′-end and 5′-end of either the sense strand, the antisensestrand, or both strands of the chemically-modified siNA molecule, or anycombination thereof. In one embodiment, a conjugate molecule of theinvention comprises a molecule that facilitates delivery of achemically-modified siNA molecule molecule into a biological system suchas a cell. In another embodiment, the conjugate molecule attached to thechemically-modified siNA molecule is a poly ethylene glycol, human serumalbumin, or a ligand for a cellular receptor that can mediate cellularuptake. Examples of specific conjugate molecules contemplated by theinstant invention that can be attached to chemically-modified siNAmolecules are described in Vargeese et al., U.S. Ser. No. 60/311,865,incorporated by reference herein. The type of conjugates used and theextent of conjugation of siNA molecules of the invention can beevaluated for improved pharmacokinetic profiles, bioavailability, and/orstability of siNA constructs while at the same time maintaining theability of the siNA to mediate RNAi activity. As such, one skilled inthe art can screen siNA constructs that are modified with variousconjugates to determine whether the siNA conjugate complex possessesimproved properties while maintaining the ability to mediate RNAi, forexample in animal models as are generally known in the art.

In one embodiment, the invention features a short interfering nucleicacid (siNA) molecule of the invention, wherein the siNA furthercomprises a nucleotide, non-nucleotide, or mixednucleotide/non-nucleotide linker that joins the sense region of the siNAto the antisense region of the siNA. In another embodiment, a nucleotidelinker of the invention can be a linker of ≧2 nucleotides in length, forexample 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides in length. In yet anotherembodiment, the nucleotide linker can be a nucleic acid aptamer. By“aptamer” or “nucleic acid aptamer” as used herein is meant a nucleicacid molecule that binds specifically to a target molecule wherein thenucleic acid molecule has sequence that is comprises a sequencerecognized by the target molecule in its natural setting. Alternately,an aptamer can be a nucleic acid molecule that binds to a targetmolecule where the target molecule does not naturally bind to a nucleicacid. The target molecule can be any molecule of interest. For example,the aptamer can be used to bind to a ligand-binding domain of a protein,thereby preventing interaction of the naturally occurring ligand withthe protein. This is a non-limiting example and those in the art willrecognize that other embodiments can be readily generated usingtechniques generally known in the art, see for example Gold et al.,1995, Annu. Rev. Biochem., 64, 763; Brody and Gold, 2000, J.Biotechnol., 74, 5; Sun, 2000, Curr. Opin. Mol. Ther., 2, 100; Kusser,2000, J. Biotechnol., 74, 27; Hermann and Patel, 2000, Science, 287,820; and Jayasena, 1999, Clinical Chemistry, 45, 1628.

In yet another embodiment, a non-nucleotide linker of the inventioncomprises abasic nucleotide, polyether, polyamine, polyamide, peptide,carbohydrate, lipid, polyhydrocarbon, or other polymeric compounds (e.g.polyethylene glycols such as those having between 2 and 100 ethyleneglycol units). Specific examples include those described by Seela andKaiser, Nucleic Acids Res. 1990, 18:6353 and Nucleic Acids Res. 1987,15:3113; Cload and Schepartz, J. Am. Chem. Soc. 1991, 113:6324;Richardson and Schepartz, J. Am. Chem. Soc. 1991, 113:5109; Ma et al.,Nucleic Acids Res. 1993, 21:2585 and Biochemistry 1993, 32:1751; Durandet al., Nucleic Acids Res. 1990, 18:6353; McCurdy et al., Nucleosides &Nucleotides 1991, 10:287; Jschke et al., Tetrahedron Lett. 1993, 34:301;Ono et al., Biochemistry 1991, 30:9914; Arnold et al., InternationalPublication No. WO 89/02439; Usman et al., International Publication No.WO 95/06731; Dudycz et al., International Publication No. WO 95/11910and Ferentz and Verdine, J. Am. Chem. Soc. 1991, 113:4000, all herebyincorporated by reference herein. A “non-nucleotide” further means anygroup or compound that can be incorporated into a nucleic acid chain inthe place of one or more nucleotide units, including either sugar and/orphosphate substitutions, and allows the remaining bases to exhibit theirenzymatic activity. The group or compound can be abasic in that it doesnot contain a commonly recognized nucleotide base, such as adenosine,guanine, cytosine, uracil or thymine, for example at the C1 position ofthe sugar.

In one embodiment, the invention features a short interfering nucleicacid (siNA) molecule capable of mediating RNA interference (RNAi) insidea cell or reconstituted in vitro system, wherein one or both strands ofthe siNA molecule that are assembled from two separate oligonucleotidesdo not comprise any ribonucleotides. All positions within the siNA caninclude chemically modified nucleotides and/or non-nucleotides such asnucleotides and or non-nucleotides having Formula I, II, III, IV, V, VI,or VII or any combination thereof to the extent that the ability of thesiNA molecule to support RNAi activity in a cell is maintained.

In one embodiment, a siNA molecule of the invention is a single strandedsiNA molecule that mediates RNAi activity in a cell or reconstituted invitro system, wherein the siNA molecule comprises a single strandedoligonucleotide having complementarity to a target nucleic acidsequence. In another embodiment, the single stranded siNA molecule ofthe invention comprises a 5′-terminal phosphate group. In anotherembodiment, the single stranded siNA molecule of the invention comprisesa 5′-terminal phosphate group and a 3′-terminal phosphate group (e.g., a2′,3′-cyclic phosphate). In another embodiment, the single stranded siNAmolecule of the invention comprises between 19 and 29 nucleotides. Inyet another embodiment, the single stranded siNA molecule of theinvention comprises one or more chemically modified nucleotides ornon-nucleotides described herein. For example, all the positions withinthe siNA molecule can include chemically-modified nucleotides such asnucleotides having any of Formulae I-VII, or any combination thereof tothe extent that the ability of the siNA molecule to support RNAiactivity in a cell is maintained.

In one embodiment, a siNA molecule of the invention is a single strandedsiNA molecule that mediates RNAi activity in a cell or reconstituted invitro system, wherein the siNA molecule comprises a single strandedoligonucleotide having complementarity to a target nucleic acidsequence, and wherein one or more pyrimidine nucleotides present in thesiNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein allpyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides oralternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides), and wherein any purine nucleotides present inthe antisense region are 2′-O-methyl purine nucleotides (e.g., whereinall purine nucleotides are 2′-O-methyl purine nucleotides or alternatelya plurality of purine nucleotides are 2′-O-methyl purine nucleotides),and a terminal cap modification, such as any modification describedherein, that is optionally present at the 3′-end, the 5′-end, or both ofthe 3′ and 5′-ends of the antisense sequence, the siNA optionallyfurther comprising between about 1 and about 4 (e.g, about 1, 2, 3, or4) terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule,wherein the terminal nucleotides can further comprise one or more (e.g.,1, 2, 3, or 4) phosphorothioate internucleotide linkages, and whereinthe siNA optionally further comprises a terminal phosphate group, suchas a 5′-terminal phosphate group.

In one embodiment, a siNA molecule of the invention is a single strandedsiNA molecule that mediates RNAi activity in a cell or reconstituted invitro system, wherein the siNA molecule comprises a single strandedoligonucleotide having complementarity to a target nucleic acidsequence, and wherein one or more pyrimidine nucleotides present in thesiNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein allpyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides oralternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides), and wherein any purine nucleotides present inthe antisense region are 2′-deoxy purine nucleotides (e.g., wherein allpurine nucleotides are 2′-deoxy purine nucleotides or alternately aplurality of purine nucleotides are 2′-deoxy purine nucleotides), and aterminal cap modification, such as any modification described herein,that is optionally present at the 3′-end, the 5′-end, or both of the 3′and 5′-ends of the antisense sequence, the siNA optionally furthercomprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4)terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, whereinthe terminal nucleotides can further comprise one or more (e.g., 1, 2,3, or 4) phosphorothioate internucleotide linkages, and wherein the siNAoptionally further comprises a terminal phosphate group, such as a5′-terminal phosphate group.

In one embodiment, a siNA molecule of the invention is a single strandedsiNA molecule that mediates RNAi activity in a cell or reconstituted invitro system, wherein the siNA molecule comprises a single strandedoligonucleotide having complementarity to a target nucleic acidsequence, and wherein one or more pyrimidine nucleotides present in thesiNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein allpyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides oralternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides), and wherein any purine nucleotides present inthe antisense region are locked nucleic acid (LNA) nucleotides (e.g.,wherein all purine nucleotides are LNA nucleotides or alternately aplurality of purine nucleotides are LNA nucleotides), and a terminal capmodification, such as any modification described herein, that isoptionally present at the 3′-end, the 5′-end, or both of the 3′ and5′-ends of the antisense sequence, the siNA optionally furthercomprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4)terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, whereinthe terminal nucleotides can further comprise one or more (e.g., 1, 2,3, or 4) phosphorothioate internucleotide linkages, and wherein the siNAoptionally further comprises a terminal phosphate group, such as a5′-terminal phosphate group.

In one embodiment, a siNA molecule of the invention is a single strandedsiNA molecule that mediates RNAi activity in a cell or reconstituted invitro system, wherein the siNA molecule comprises a single strandedoligonucleotide having complementarity to a target nucleic acidsequence, and wherein one or more pyrimidine nucleotides present in thesiNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein allpyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides oralternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides), and wherein any purine nucleotides present inthe antisense region are 2′-methoxyethyl purine nucleotides (e.g.,wherein all purine nucleotides are 2′-methoxyethyl purine nucleotides oralternately a plurality of purine nucleotides are 2′-methoxyethyl purinenucleotides), and a terminal cap modification, such as any modificationdescribed herein, that is optionally present at the 3′-end, the 5′-end,or both of the 3′ and 5′-ends of the antisense sequence, the siNAoptionally further comprising between about 1 and about 4 (e.g, about 1,2, 3, or 4) terminal 2′-deoxynucleotides at the 3′-end of the siNAmolecule, wherein the terminal nucleotides can further comprise one ormore (e.g., 1, 2, 3, or 4) phosphorothioate internucleotide linkages,and wherein the siNA optionally further comprises a terminal phosphategroup, such as a 5′-terminal phosphate group.

In one embodiment, a siNA molecule of the invention is a single strandedsiNA molecule that mediates RNAi activity in a cell or reconstituted invitro system, wherein the siNA molecule comprises a single strandedoligonucleotide having complementarity to a target nucleic acidsequence, and wherein one or more pyrimidine nucleotides present in thesiNA are 2′-deoxy-2′-fluoro pyrimidine nucleotides (e.g., wherein allpyrimidine nucleotides are 2′-deoxy-2′-fluoro pyrimidine nucleotides oralternately a plurality of pyrimidine nucleotides are 2′-deoxy-2′-fluoropyrimidine nucleotides), and wherein any purine nucleotides present inthe antisense region are purine ribonucleotides (e.g., wherein allpurine nucleotides are purine ribonucleotides or alternately a pluralityof purine nucleotides are purine ribonucleotides), and a terminal capmodification, such as any modification described herein, that isoptionally present at the 3′-end, the 5′-end, or both of the 3′ and5′-ends of the antisense sequence, the siNA optionally furthercomprising between about 1 and about 4 (e.g, about 1, 2, 3, or 4)terminal 2′-deoxynucleotides at the 3′-end of the siNA molecule, whereinthe terminal nucleotides can further comprise one or more (e.g., 1, 2,3, or 4) phosphorothioate internucleotide linkages, and wherein the siNAoptionally further comprises a terminal phosphate group, such as a5′-terminal phosphate group.

In another embodiment, any modified nucleotides present in the singlestranded siNA molecules of the invention comprise modified nucleotideshaving properties or characteristics similar to naturally occurringribonucleotides. For example, the invention features siNA moleculesincluding modified nucleotides having a Northern conformation (e.g.,Northern pseudorotation cycle, see for example Saenger, Principles ofNucleic Acid Structure, Springer-Verlag ed., 1984). As such, chemicallymodified nucleotides present in the single stranded siNA molecules ofthe invention are preferably resistant to nuclease degradation while atthe same time maintaining the capacity to mediate RNAi.

E. Preparation of Oligonucleotides

The present oligonucleotides can be prepared by methods available tothose skilled in the art. For example, unmodified RNA can be prepared bytranscription, e.g., in vitro, using methods and constructs available inthe art. The sequence for the particular target, and its complementarysequence can be inserted into a selected vector, and transcribed toproduce the desired oligonucleotides by conventional methods.

In many cases, it will be desirable to chemically synthesize theoligonucleotides, e.g., for chemically modified oligonucleotides. Suchsyntheses are known in the art, and are described, for example, below.

Thus, siNA molecules can be designed to interact with various sites inthe RNA message, for example target sequences within the RNA sequencesdescribed herein. The sequence of one strand of the siNA molecule(s) iscomplementary to the target site sequences described above. The siNAmolecules can be chemically synthesized using methods described herein.Inactive siNA molecules that are used as control sequences can besynthesized by scrambling the sequence of the siNA molecules such thatit is not complementary to the target sequence. Generally, siNAconstructs can by synthesized using solid phase oligonucleotidesynthesis methods as described herein (see for example Usman et al.,U.S. Pat. Nos. 5,804,683; 5,831,071; 5,998,203; 6,117,657; 6,353,098;6,362,323; 6,437,117; 6,469,158; Scaringe et al., U.S. Pat. Nos.6,111,086; 6,008,400; 6,111,086). Modification of synthesis conditionscan be used to optimize coupling efficiency, for example by usingdiffering coupling times, differing reagent/phosphoramiditeconcentrations, differing contact times, differing solid supports andsolid support linker chemistries depending on the particular chemicalcomposition of the siNA to be synthesized. Deprotection and purificationof the siNA can be performed as is generally described in Vargeese etal., U.S. Ser. No. 10/194,875, incorporated by reference herein in itsentirety. Additionally, deprotection conditions can be modified toprovide the best possible yield and purity of siNA constructs. Forexample, applicant has observed that oligonucleotides comprising2′-deoxy-2′-fluoro nucleotides can degrade under inappropriatedeprotection conditions. Such oligonucleotides are deprotected usingaqueous methylamine at about 35° C. for 30 minutes. If the2′-deoxy-2′-fluoro containing oligonucleotide also comprisesribonucleotides, after deprotection with aqueous methylamine at about35° C. for 30 minutes, TEA-HF is added and the reaction maintained atabout 65° C. for an additional 15 minutes.

Synthesis of Nucleic Acid Molecules

In greater detail, synthesis of nucleic acids greater than 100nucleotides in length is difficult using automated methods, and thetherapeutic cost of such molecules is prohibitive. In this invention,small nucleic acid motifs, “small” refers to nucleic acid motifs no morethan 100 nucleotides in length, preferably no more than 80 nucleotidesin length, and most preferably no more than 50 nucleotides in length;e.g., individual siNA oligonucleotide sequences or siNA sequencessynthesized in tandem) are preferably used for exogenous delivery. Thesimple structure of these molecules increases the ability of the nucleicacid to invade targeted regions of protein and/or RNA structure.Exemplary molecules of the instant invention are chemically synthesized,and others can similarly be synthesized.

Oligonucleotides (e.g., certain modified oligonucleotides or portions ofoligonucleotides lacking ribonucleotides) are synthesized usingprotocols known in the art, for example as described in Caruthers etal., 1992, Methods in Enzymology 211, 3-19, Thompson et al.,International PCT Publication No. WO 99/54459, Wincott et al., 1995,Nucleic Acids Res. 23, 2677-2684, Wincott et al., 1997, Methods Mol.Bio., 74, 59, Brennan et al., 1998, Biotechnol Bioeng., 61, 33-45, andBrennan, U.S. Pat. No. 6,001,311. All of these references areincorporated herein by reference. The synthesis of oligonucleotidesmakes use of common nucleic acid protecting and coupling groups, such asdimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. In anon-limiting example, small scale syntheses are conducted on a 394Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocolwith a 2.5 min coupling step for 2′-O-methylated nucleotides and a 45sec coupling step for 2′-deoxy nucleotides or 2′-deoxy-2′-fluoronucleotides. Alternatively, syntheses at the 0.2 μmol scale can beperformed on a 96-well plate synthesizer, such as the instrumentproduced by Protogene (Palo Alto, Calif.) with minimal modification tothe cycle. A 33-fold excess (60 μL of 0.11 M=6.6 μmol) of 2′-O-methylphosphoramidite and a 105-fold excess of S-ethyl tetrazole (60 μL of0.25 M=15 μmol) can be used in each coupling cycle of 2′-O-methylresidues relative to polymer-bound 5′-hydroxyl. A 22-fold excess (40 μLof 0.11 M=4.4 mmol) of deoxy phosphoramidite and a 70-fold excess ofS-ethyl tetrazole (40 μL of 0.25 M=10 μmol) can be used in each couplingcycle of deoxy residues relative to polymer-bound 5′-hydroxyl. Averagecoupling yields on the 394 Applied Biosystems, Inc. synthesizer,determined by colorimetric quantitation of the trityl fractions, aretypically 97.5-99%. Other oligonucleotide synthesis reagents for the 394Applied Biosystems, Inc. synthesizer include the following:detritylation solution is 3% TCA in methylene chloride (ABI); capping isperformed with 16% N-methyl imidazole in THF (ABI) and 10% aceticanhydride/10% 2,6-lutidine in THF (ABI); and oxidation solution is 16.9mM I₂, 49 mM pyridine, 9% water in THF (PERSEPTIVE™). Burdick & JacksonSynthesis Grade acetonitrile is used directly from the reagent bottle.S-Ethyltetrazole solution (0.25 M in acetonitrile) is made up from thesolid obtained from American International Chemical, Inc. Alternately,for the introduction of phosphorothioate linkages, Beaucage reagent(3H-1,2-Benzodithiol-3-one 1,1-dioxide, 0.05 M in acetonitrile) is used.

Deprotection of the DNA-based oligonucleotides is performed as follows:the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mLglass screw top vial and suspended in a solution of 40% aq. methylamine(1 mL) at 65° C. for 10 min. After cooling to −20° C., the supernatantis removed from the polymer support. The support is washed three timeswith 1.0 mL of EtOH:MeCN:H2O/3:1:1, vortexed and the supernatant is thenadded to the first supernatant. The combined supernatants, containingthe oligoribonucleotide, are dried to a white powder.

The method of synthesis used for RNA including certain siNA molecules ofthe invention follows the procedure as described in Usman et al., 1987,J. Am. Chem. Soc., 109, 7845; Scaringe et al., 1990, Nucleic Acids Res.,18, 5433; and Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684Wincott et al., 1997, Methods Mol. Bio., 74, 59, and makes use of commonnucleic acid protecting and coupling groups, such as dimethoxytrityl atthe 5′-end, and phosphoramidites at the 3′-end. In a non-limitingexample, small scale syntheses are conducted on a 394 AppliedBiosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 7.5min coupling step for alkylsilyl protected nucleotides and a 2.5 mincoupling step for 2′-O-methylated nucleotides. Alternatively, synthesesat the 0.2 μmol scale can be done on a 96-well plate synthesizer, suchas the instrument produced by Protogene (Palo Alto, Calif.) with minimalmodification to the cycle. A 33-fold excess (60 μL of 0.11 M=6.6 μmol)of 2′-O-methyl phosphoramidite and a 75-fold excess of S-ethyl tetrazole(60 μL of 0.25 M=15 μmol) can be used in each coupling cycle of2′-O-methyl residues relative to polymer-bound 5′-hydroxyl. A 66-foldexcess (120 μL of 0.11 M=13.2 μmol) of alkylsilyl (ribo) protectedphosphoramidite and a 150-fold excess of S-ethyl tetrazole (120 μL of0.25 M=30 μmol) can be used in each coupling cycle of ribo residuesrelative to polymer-bound 5′-hydroxyl. Average coupling yields on the394 Applied Biosystems, Inc. synthesizer, determined by colorimetricquantitation of the trityl fractions, are typically 97.5-99%. Otheroligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc.synthesizer include the following: detritylation solution is 3% TCA inmethylene chloride (ABI); capping is performed with 16% N-methylimidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF(ABI); oxidation solution is 16.9 mM I₂, 49 mM pyridine, 9% water in THF(PERSEPTIVE™). Burdick & Jackson Synthesis Grade acetonitrile is useddirectly from the reagent bottle. S-Ethyltetrazole solution (0.25 M inacetonitrile) is made up from the solid obtained from AmericanInternational Chemical, Inc. Alternately, for the introduction ofphosphorothioate linkages, Beaucage reagent (3H-1,2-Benzodithiol-3-one1,1-dioxide 0.05 M in acetonitrile) is used.

Deprotection of the RNA is performed using either a two-pot or one-potprotocol. For the two-pot protocol, the polymer-bound trityl-onoligoribonucleotide is transferred to a 4 mL glass screw top vial andsuspended in a solution of 40% aq. methylamine (1 mL) at 65° C. for 10min. After cooling to −20° C., the supernatant is removed from thepolymer support. The support is washed three times with 1.0 mL ofEtOH:MeCN:H2O/3:1:1, vortexed and the supernatant is then added to thefirst supernatant. The combined supernatants, containing theoligoribonucleotide, are dried to a white powder. The base deprotectedoligoribonucleotide is resuspended in anhydrous TEA/HF/NMP solution (300μL of a solution of 1.5 mL N-methylpyrrolidinone, 750 μL TEA and 1 mLTEA•3HF to provide a 1.4 M HF concentration) and heated to 65° C. After1.5 h, the oligomer is quenched with 1.5 M NH₄HCO₃.

Alternatively, for the one-pot protocol, the polymer-bound trityl-onoligoribonucleotide is transferred to a 4 mL glass screw top vial andsuspended in a solution of 33% ethanolic methylamine/DMSO: 1/1 (0.8 mL)at 65° C. for 15 min. The vial is brought to r.t. TEA•3HF (0.1 mL) isadded and the vial is heated at 65° C. for 15 min. The sample is cooledat −20° C. and then quenched with 1.5 M NH₄HCO₃.

For purification of the trityl-on oligomers, the quenched NH₄HCO₃solution is loaded onto a C-18 containing cartridge that had beenprewashed with acetonitrile followed by 50 mM TEAA. After washing theloaded cartridge with water, the RNA is detritylated with 0.5% TFA for13 min. The cartridge is then washed again with water, salt exchangedwith 1 M NaCl and washed with water again. The oligonucleotide is theneluted with 30% acetonitrile.

The average stepwise coupling yields are typically >98% (Wincott et al.,1995 Nucleic Acids Res. 23, 2677-2684). Those of ordinary skill in theart will recognize that the scale of synthesis can be adapted to belarger or smaller than the example described above including but notlimited to 96-well format.

Alternatively, the nucleic acid molecules of the present invention canbe synthesized separately and joined together post-synthetically, forexample, by ligation (Moore et al., 1992, Science 256, 9923; Draper etal., International PCT publication No. WO 93/23569; Shabarova et al.,1991, Nucleic Acids Research 19, 4247; Bellon et al., 1997, Nucleosides& Nucleotides, 16, 951; Bellon et al., 1997, Bioconjugate Chem. 8, 204),or by hybridization following synthesis and/or deprotection.

The siNA molecules of the invention can also be synthesized via a tandemsynthesis methodology as described below, where both siNA strands aresynthesized as a single contiguous oligonucleotide fragment or strandseparated by a cleavable linker which is subsequently cleaved to provideseparate siNA fragments or strands that hybridize and permitpurification of the siNA duplex. The linker can be a oligonucleotidelinker or a non-nucleotide linker. The tandem synthesis of siNA asdescribed herein can be readily adapted to both multiwell/multiplatesynthesis platforms such as 96 well or similarly larger multi-wellplatforms. The tandem synthesis of siNA as described herein can also bereadily adapted to large scale synthesis platforms employing batchreactors, synthesis columns and the like.

A siNA molecule can also be assembled from two distinct nucleic acidstrands or fragments wherein one fragment includes the sense region andthe second fragment includes the antisense region of the RNA molecule.

The nucleic acid molecules of the present invention can be modifiedextensively to enhance stability by modification with nuclease resistantgroups, for example, 2′-amino, 2′-C-allyl, 2′-fluoro, 2′-O-methyl, 2′-H(for a review see Usman and Cedergren, 1992, TIBS 17, 34; Usman et al.,1994, Nucleic Acids Symp. Ser. 31, 163). siNA constructs can be purifiedby gel electrophoresis using general methods or can be purified by highpressure liquid chromatography (HPLC; see Wincott et al., supra, thetotality of which is hereby incorporated herein by reference) andre-suspended in water.

In another aspect of the invention, siNA molecules of the invention areexpressed from transcription units inserted into DNA or RNA vectors. Therecombinant vectors can be DNA plasmids or viral vectors. siNAexpressing viral vectors can be constructed based on, but not limitedto, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Therecombinant vectors capable of expressing the siNA molecules can bedelivered as described herein, and persist in target cells.Alternatively, viral vectors can be used that provide for transientexpression of siNA molecules.

Tandem Synthesis of siNA Constructs

Exemplary siNA molecules are synthesized in tandem using a cleavablelinker, for example a succinyl-based linker. Tandem synthesis asdescribed herein is followed by a one-step purification process thatprovides RNAi molecules in high yield. This approach is highly amenableto siNA synthesis in support of high throughput RNAi screening, and canbe readily adapted to multi-column or multi-well synthesis platforms.

After completing a tandem synthesis of an siNA oligo and its complementin which the 5′-terminal dimethoxytrityl (5′-O-DMT) group remains intact(trityl on synthesis), the oligonucleotides are deprotected as describedabove. Following deprotection, the siNA sequence strands are allowed tospontaneously hybridize. This hybridization yields a duplex in which onestrand has retained the 5′-O-DMT group while the complementary strandcomprises a terminal 5′-hydroxyl. The newly formed duplex behaves as asingle molecule during routine solid-phase extraction purification(Trityl-On purification) even though only one molecule has adimethoxytrityl group. Because the strands form a stable duplex, thisdimethoxytrityl group (or an equivalent group, such as other tritylgroups or other hydrophobic moieties) is all that is required to purifythe pair of oligos, for example by using a C18 cartridge.

Standard phosphoramidite synthesis chemistry is used up to point ofintroducing a tandem linker, such as an inverted deoxy abasic succinateor glyceryl succinate linker or an equivalent cleavable linker. Anon-limiting example of linker coupling conditions that can be usedincludes a hindered base such as diisopropylethylamine (DIPA) and/orDMAP in the presence of an activator reagent such asBromotripyrrolidinophosphoniumhexafluororophosphate (PyBrOP). After thelinker is coupled, standard synthesis chemistry is utilized to completesynthesis of the second sequence leaving the terminal the 5′-O-DMTintact. Following synthesis, the resulting oligonucleotide isdeprotected according to the procedures described herein and quenchedwith a suitable buffer, for example with 50 mM NaOAc or 1.5M NH₄H₂CO₃.

Purification of the siNA duplex can be readily accomplished using solidphase extraction, for example using a Waters C18 SepPak 1 g cartridgeconditioned with 1 column volume (CV) of acetonitrile, 2 CV H2O, and 2CV 50 mM NaOAc: The sample is loaded and then washed with 1 CV H2O or 50mM NaOAc. Failure sequences are eluted with 1 CV 14% ACN (Aqueous with50 mM NaOAc and 50 mM NaCl). The column is then washed, for example with1 CV H2O followed by on-column detritylation, for example by passing 1CV of 1% aqueous trifluoroacetic acid (TFA) over the column, then addinga second CV of 1% aqueous TFA to the column and allowing to stand forapprox. 10 minutes. The remaining TFA solution is removed and the columnwashed with H2O followed by 1 CV 1 M NaCl and additional H2O. The siNAduplex product is then eluted, for example using 1 CV 20% aqueous CAN.

Optimizing Activity of the Nucleic Acid Molecules.

Chemically synthesizing nucleic acid molecules with modifications (base,sugar and/or phosphate) can prevent their degradation by serumribonucleases, which can increase their potency (see e.g., Eckstein etal., International Publication No. WO 92/07065; Perrault et al., 1990Nature 344, 565; Pieken et al., 1991, Science 253, 314; Usman andCedergren, 1992, Trends in Biochem. Sci. 17, 334; Usman et al.,International Publication No. WO 93/15187; and Rossi et al.,International Publication No. WO 91/03162; Sproat, U.S. Pat. No.5,334,711; Gold et al., U.S. Pat. No. 6,300,074; and Burgin et al.,supra; all of which are incorporated by reference herein). All of theabove references describe various chemical modifications that can bemade to the base, phosphate and/or sugar moieties of the nucleic acidmolecules described herein. Modifications that enhance their efficacy incells, and removal of bases from nucleic acid molecules to shortenoligonucleotide synthesis times and reduce chemical requirements aredesired.

There are several examples in the art describing sugar, base andphosphate modifications that can be introduced into nucleic acidmolecules with significant enhancement in their nuclease stability andefficacy. For example, oligonucleotides are modified to enhancestability and/or enhance biological activity by modification withnuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-fluoro,2′-O-methyl, 2′-O-allyl, 2′-H, nucleotide base modifications (for areview see Usman and Cedergren, 1992, TIBS. 17, 34; Usman et al., 1994,Nucleic Acids Symp. Ser. 31, 163; Burgin et al., 1996, Biochemistry, 35,14090). Sugar modification of nucleic acid molecules have beenextensively described in the art (see Eckstein et al., InternationalPublication PCT No. WO 92/07065; Perrault et al. Nature, 1990, 344,565-568; Pieken et al. Science, 1991, 253, 314-317; Usman and Cedergren,Trends in Biochem. Sci., 1992, 17, 334-339; Usman et al. InternationalPublication PCT No. WO 93/15187; Sproat, U.S. Pat. No. 5,334,711 andBeigelman et al., 1995, J. Biol. Chem., 270, 25702; Beigelman et al.,International PCT publication No. WO 97/26270; Beigelman et al., U.S.Pat. No. 5,716,824; Usman et al., U.S. Pat. No. 5,627,053; Woolf et al.,International PCT Publication No. WO 98/13526; Thompson et al., U.S.Ser. No. 60/082,404 which was filed on Apr. 20, 1998; Karpeisky et al.,1998, Tetrahedron Lett., 39, 1131; Earnshaw and Gait, 1998, Biopolymers(Nucleic Acid Sciences), 48, 39-55; Verma and Eckstein, 1998, Annu. Rev.Biochem., 67, 99-134; and Burlina et al., 1997, Bioorg. Med. Chem., 5,1999-2010; all of the references are hereby incorporated in theirtotality by reference herein). Such publications describe generalmethods and strategies to determine the location of incorporation ofsugar, base and/or phosphate modifications and the like into nucleicacid molecules without modulating catalysis, and are incorporated byreference herein. In view of such teachings, similar modifications canbe used as described herein to modify the siNA nucleic acid molecules ofthe instant invention so long as the ability of siNA to promote RNAi iscells is not significantly inhibited.

While chemical modification of oligonucleotide internucleotide linkageswith phosphorothioate, phosphorodithioate, and/or 5′-methylphosphonatelinkages improves stability, excessive modifications can cause sometoxicity or decreased activity. Therefore, when designing nucleic acidmolecules, the amount of these internucleotide linkages should beminimized. The reduction in the concentration of these linkages shouldlower toxicity, resulting in increased efficacy and higher specificityof these molecules.

Short interfering nucleic acid (siNA) molecules having chemicalmodifications that maintain or enhance activity are provided. Such anucleic acid is also generally more resistant to nucleases than anunmodified nucleic acid. Accordingly, the in vitro and/or in vivoactivity should not be significantly lowered. In cases in whichmodulation is the goal, therapeutic nucleic acid molecules deliveredexogenously should optimally be stable within cells until translation ofthe target RNA has been modulated long enough to reduce the levels ofthe undesirable protein. This period of time varies between hours todays depending upon the disease state. Improvements in the chemicalsynthesis of RNA and DNA (Wincott et al., 1995, Nucleic Acids Res. 23,2677; Caruthers et al., 1992, Methods in Enzymology 211, 3-19(incorporated by reference herein)) have expanded the ability to modifynucleic acid molecules by introducing nucleotide modifications toenhance their nuclease stability, as described above.

In one embodiment, nucleic acid molecules of the invention include oneor more (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) G-clampnucleotides. A G-clamp nucleotide is a modified cytosine analog whereinthe modifications confer the ability to hydrogen bond both Watson-Crickand Hoogsteen faces of a complementary guanine within a duplex, see forexample Lin and Matteucci, 1998, J. Am. Chem. Soc., 120, 8531-8532. Asingle G-clamp analog substitution within an oligonucleotide can resultin substantially enhanced helical thermal stability and mismatchdiscrimination when hybridized to complementary oligonucleotides. Theinclusion of such nucleotides in nucleic acid molecules of the inventionresults in both enhanced affinity and specificity to nucleic acidtargets, complementary sequences, or template strands. In anotherembodiment, nucleic acid molecules of the invention include one or more(e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more) LNA “locked nucleicacid” nucleotides such as a 2′,4′-C mythylene bicyclo nucleotide (seefor example Wengel et al., International PCT Publication No. WO 00/66604and WO 99/14226).

In another embodiment, the invention features conjugates and/orcomplexes of siNA molecules of the invention. Such conjugates and/orcomplexes can be used to facilitate delivery of siNA molecules into abiological system, such as a cell. The conjugates and complexes providedby the instant invention can impart therapeutic activity by transferringtherapeutic compounds across cellular membranes, altering thepharmacokinetics, and/or modulating the localization of nucleic acidmolecules of the invention. The present invention encompasses the designand synthesis of novel conjugates and complexes for the delivery ofmolecules, including, but not limited to, small molecules, lipids,phospholipids, nucleosides, nucleotides, nucleic acids, antibodies,toxins, negatively charged polymers and other polymers, for exampleproteins, peptides, hormones, carbohydrates, polyethylene glycols, orpolyamines, across cellular membranes. In general, the transportersdescribed are designed to be used either individually or as part of amulti-component system, with or without degradable linkers. Thesecompounds are expected to improve delivery and/or localization ofnucleic acid molecules of the invention into a number of cell typesoriginating from different tissues, in the presence or absence of serum(see Sullenger and Cech, U.S. Pat. No. 5,854,038). Conjugates of themolecules described herein can be attached to biologically activemolecules via linkers that are biodegradable, such as biodegradablenucleic acid linker molecules.

The term “biodegradable linker” as used herein, refers to a nucleic acidor non-nucleic acid linker molecule that is designed as a biodegradablelinker to connect one molecule to another molecule, for example, abiologically active molecule to a siNA molecule of the invention or thesense and antisense strands of a siNA molecule of the invention. Thebiodegradable linker is designed such that its stability can bemodulated for a particular purpose, such as delivery to a particulartissue or cell type. The stability of a nucleic acid-based biodegradablelinker molecule can be modulated by using various chemistries, forexample combinations of ribonucleotides, deoxyribonucleotides, andchemically-modified nucleotides, such as 2′-O-methyl, 2′-fluoro,2′-amino, 2′-O-amino, 2′-C-allyl, 2′-O-allyl, and other 2′-modified orbase modified nucleotides. The biodegradable nucleic acid linkermolecule can be a dimer, trimer, tetramer or longer nucleic acidmolecule, for example, an oligonucleotide of about 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides in length,or can comprise a single nucleotide with a phosphorus-based linkage, forexample, a phosphoramidate or phosphodiester linkage. The biodegradablenucleic acid linker molecule can also comprise nucleic acid backbone,nucleic acid sugar, or nucleic acid base modifications.

The term “biodegradable” as used herein, refers to degradation in abiological system, for example enzymatic degradation or chemicaldegradation.

The term “biologically active molecule” as used herein, refers tocompounds or molecules that are capable of eliciting or modifying abiological response in a system. Non-limiting examples of biologicallyactive siNA molecules either alone or in combination with othermolecules contemplated by the instant invention include therapeuticallyactive molecules such as antibodies, hormones, antivirals, peptides,proteins, chemotherapeutics, small molecules, vitamins, co-factors,nucleosides, nucleotides, oligonucleotides, enzymatic nucleic acids,antisense nucleic acids, triplex forming oligonucleotides, 2,5-Achimeras, siNA, dsRNA, allozymes, aptamers, decoys and analogs thereof.Biologically active molecules of the invention also include moleculescapable of modulating the pharmacokinetics and/or pharmacodynamics ofother biologically active molecules, for example, lipids and polymerssuch as polyamines, polyamides, polyethylene glycol and otherpolyethers.

The term “phospholipid” as used herein, refers to a hydrophobic moleculecomprising at least one phosphorus group. For example, a phospholipidcan comprise a phosphorus-containing group and saturated or unsaturatedalkyl group, optionally substituted with OH, COOH, oxo, amine, orsubstituted or unsubstituted aryl groups.

Therapeutic nucleic acid molecules (e.g., siNA molecules) deliveredexogenously optimally are stable within cells until reversetranscription of the RNA has been modulated long enough to reduce thelevels of the RNA transcript. The nucleic acid molecules are resistantto nucleases in order to function as effective intracellular therapeuticagents. Improvements in the chemical synthesis of nucleic acid moleculesdescribed in the instant invention and in the art have expanded theability to modify nucleic acid molecules by introducing nucleotidemodifications to enhance their nuclease stability as described above.

In yet another embodiment, siNA molecules having chemical modificationsthat maintain or enhance enzymatic activity of proteins involved in RNAiare provided. Such nucleic acids are also generally more resistant tonucleases than unmodified nucleic acids. Thus, in vitro and/or in vivothe activity should not be significantly lowered.

Use of the nucleic acid-based molecules of the invention will lead tobetter treatment of the disease progression by affording the possibilityof combination therapies (e.g., multiple siNA molecules targeted todifferent genes; nucleic acid molecules coupled with known smallmolecule modulators; or intermittent treatment with combinations ofmolecules, including different motifs and/or other chemical orbiological molecules). The treatment of subjects with siNA molecules canalso include combinations of different types of nucleic acid molecules,such as enzymatic nucleic acid molecules (ribozymes), allozymes,antisense, 2,5-A oligoadenylate, decoys, and aptamers.

In another aspect a siNA molecule of the invention comprises one or more5′ and/or a 3′-cap structure, for example on only the sense siNA strand,the antisense siNA strand, or both siNA strands.

By “cap structure” is meant chemical modifications, which have beenincorporated at either terminus of the oligonucleotide (see, forexample, Adamic et al., U.S. Pat. No. 5,998,203, incorporated byreference herein). These terminal modifications protect the nucleic acidmolecule from exonuclease degradation, and may help in delivery and/orlocalization within a cell. The cap may be present at the 5′-terminus(5′-cap) or at the 3′-terminal (3′-cap) or may be present on bothtermini. In non-limiting examples: the 5′-cap is selected from the groupcomprising glyceryl, inverted deoxy abasic residue (moiety);4′,5′-methylene nucleotide; 1-(beta-D-erythrofuranosyl) nucleotide,4′-thio nucleotide; carbocyclic nucleotide; 1,5-anhydrohexitolnucleotide; L-nucleotides; alpha-nucleotides; modified base nucleotide;phosphorodithioate linkage; threo-pentofuranosyl nucleotide; acyclic3′,4′-seco nucleotide; acyclic 3,4-dihydroxybutyl nucleotide; acyclic3,5-dihydroxypentyl nucleotide, 3′-3′-inverted nucleotide moiety;3′-3′-inverted abasic moiety; 3′-2′-inverted nucleotide moiety;3′-2′-inverted abasic moiety; 1,4-butanediol phosphate;3′-phosphoramidate; hexylphosphate; aminohexyl phosphate; 3′-phosphate;3′-phosphorothioate; phosphorodithioate; or bridging or non-bridgingmethylphosphonate moiety.

In yet another embodiment, the 3′-cap is selected from a groupcomprising glyceryl, inverted deoxy abasic residue (moiety),4′,5′-methylene nucleotide; I-(beta-D-erythrofuranosyl) nucleotide;4′-thio nucleotide, carbocyclic nucleotide; 5′-amino-alkyl phosphate;1,3-diamino-2-propyl phosphate; 3-aminopropyl phosphate; 6-aminohexylphosphate; 1,2-aminododecyl phosphate; hydroxypropyl phosphate;1,5-anhydrohexitol nucleotide; L-nucleotide; alpha-nucleotide; modifiedbase nucleotide; phosphorodithioate; threo-pentofuranosyl nucleotide;acyclic 3′,4′-seco nucleotide; 3,4-dihydroxybutyl nucleotide;3,5-dihydroxypentyl nucleotide, 5′-5′-inverted nucleotide moiety;5′-5′-inverted abasic moiety; 5′-phosphoramidate; 5′-phosphorothioate;1,4-butanediol phosphate; 5′-amino; bridging and/or non-bridging5′-phosphoramidate, phosphorothioate and/or phosphorodithioate, bridgingor non bridging methylphosphonate and 5′-mercapto moieties (for moredetails see Beaucage and Iyer, 1993, Tetrahedron 49, 1925; incorporatedby reference herein).

By the term “non-nucleotide” is meant any group or compound which can beincorporated into a nucleic acid chain in the place of one or morenucleotide units, including either sugar and/or phosphate substitutions,and allows the remaining bases to exhibit their enzymatic activity. Thegroup or compound is abasic in that it does not contain a commonlyrecognized nucleotide base, such as adenosine, guanine, cytosine, uracilor thymine and therefore lacks a base at the 1′-position.

An “alkyl” group refers to a saturated aliphatic hydrocarbon, includingstraight-chain, branched-chain, and cyclic alkyl groups. Preferably, thealkyl group has 1 to 12 carbons. More preferably, it is a lower alkyl offrom 1 to 7 carbons, more preferably 1 to 4 carbons. The alkyl group canbe substituted or unsubstituted. When substituted the substitutedgroup(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO2 or N(CH₃)₂,amino, or SH. The term also includes alkenyl groups that are unsaturatedhydrocarbon groups containing at least one carbon-carbon double bond,including straight-chain, branched-chain, and cyclic groups. Preferably,the alkenyl group has 1 to 12 carbons. More preferably, it is a loweralkenyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. Thealkenyl group may be substituted or unsubstituted. When substituted thesubstituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S,NO₂, halogen, N(CH₃)₂, amino, or SH. The term “alkyl” also includesalkynyl groups that have an unsaturated hydrocarbon group containing atleast one carbon-carbon triple bond, including straight-chain,branched-chain, and cyclic groups. Preferably, the alkynyl group has 1to 12 carbons. More preferably, it is a lower alkynyl of from 1 to 7carbons, more preferably 1 to 4 carbons. The alkynyl group may besubstituted or unsubstituted. When substituted the substituted group(s)is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO₂ or N(CH₃)₂, amino orSH.

Such alkyl groups can also include aryl, alkylaryl, carbocyclic aryl,heterocyclic aryl, amide and ester groups. An “aryl” group refers to anaromatic group that has at least one ring having a conjugated pielectron system and includes carbocyclic aryl, heterocyclic aryl andbiaryl groups, all of which may be optionally substituted. The preferredsubstituent(s) of aryl groups are halogen, trihalomethyl, hydroxyl, SH,OH, cyano, alkoxy, alkyl, alkenyl, alkynyl, and amino groups. An“alkylaryl” group refers to an alkyl group (as described above)covalently joined to an aryl group (as described above). Carbocyclicaryl groups are groups wherein the ring atoms on the aromatic ring areall carbon atoms. The carbon atoms are optionally substituted.Heterocyclic aryl groups are groups having from 1 to 3 heteroatoms asring atoms in the aromatic ring and the remainder of the ring atoms arecarbon atoms. Suitable heteroatoms include oxygen, sulfur, and nitrogen,and include furanyl, thienyl, pyridyl, pyrrolyl, N-lower alkyl pyrrolo,pyrimidyl, pyrazinyl, imidazolyl and the like, all optionallysubstituted. An “amide” refers to an —C(O)—NH—R, where R is eitheralkyl, aryl, alkylaryl or hydrogen. An “ester” refers to an —C(O)—OR′,where R is either alkyl, aryl, alkylaryl or hydrogen.

By “nucleotide” as used herein is as recognized in the art to includenatural bases (standard), and modified bases well known in the art. Suchbases are generally located at the 1′ position of a nucleotide sugarmoiety. Nucleotides generally comprise a base, sugar and a phosphategroup. The nucleotides can be unmodified or modified at the sugar,phosphate and/or base moiety, (also referred to interchangeably asnucleotide analogs, modified nucleotides, non-natural nucleotides,non-standard nucleotides and other; see, for example, Usman andMcSwiggen, supra; Eckstein et al., International PCT Publication No. WO92/07065; Usman et al., International PCT Publication No. WO 93/15187;Uhlman & Peyman, supra, all are hereby incorporated by referenceherein). There are several examples of modified nucleic acid bases knownin the art as summarized by Limbach et al., 1994, Nucleic Acids Res. 22,2183. Some of the non-limiting examples of base modifications that canbe introduced into nucleic acid molecules include, inosine, purine,pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2,4,6-trimethoxybenzene, 3-methyl uracil, dihydrouridine, naphthyl, aminophenyl,5-alkylcytidines (e.g., 5-methylcytidine), 5-alkyluridines (e.g.,ribothymidine), 5-halouridine (e.g., 5-bromouridine) or 6-azapyrimidinesor 6-alkylpyrimidines (e.g. 6-methyluridine), propyne, and others(Burgin et al., 1996, Biochemistry, 35, 14090; Uhlman & Peyman, supra).By “modified bases” in this aspect is meant nucleotide bases other thanadenine, guanine, cytosine and uracil at 1′ position or theirequivalents.

In one embodiment, the invention features modified siNA molecules, withphosphate backbone modifications comprising one or morephosphorothioate, phosphorodithioate, methylphosphonate,phosphotriester, morpholino, amidate carbamate, carboxymethyl,acetamidate, polyamide, sulfonate, sulfonamide, sulfamate, formacetal,thioformacetal, and/or alkylsilyl, substitutions. For a review ofoligonucleotide backbone modifications, see Hunziker and Leumann, 1995,Nucleic Acid Analogues: Synthesis and Properties, in Modern SyntheticMethods, VCH, 331-417, and Mesmaeker et al., 1994, Novel BackboneReplacements for Oligonucleotides, in Carbohydrate Modifications inAntisense Research, ACS, 24-39.

By “abasic” is meant sugar moieties lacking a base or having otherchemical groups in place of a base at the 1′ position, see for exampleAdamic et al., U.S. Pat. No. 5,998,203.

By “unmodified nucleoside” is meant one of the bases adenine, cytosine,guanine, thymine, or uracil joined to the 1′ carbon ofβ-D-ribo-furanose.

By “modified nucleoside” is meant any nucleotide base which contains amodification in the chemical structure of an unmodified nucleotide base,sugar and/or phosphate. Non-limiting examples of modified nucleotidesare shown by Formulae I-VII and/or other modifications described herein.

In connection with 2′-modified nucleotides as described for the presentinvention, by “amino” is meant 2′—NH₂ or 2′-O—NH₂, which may be modifiedor unmodified. Such modified groups are described, for example, inEckstein et al., U.S. Pat. No. 5,672,695 and Matulic-Adamic et al., U.S.Pat. No. 6,248,878, which are both incorporated by reference in theirentireties.

Various modifications to nucleic acid siNA structure can be made toenhance the utility of these molecules. Such modifications will enhanceshelf-life, half-life in vitro, stability, and ease of introduction ofsuch oligonucleotides to the target site, e.g., to enhance penetrationof cellular membranes, and confer the ability to recognize and bind totargeted cells.

F. Compositions for Administration

Suitable pharmaceutical compositions containing the present RNAiinducing oligonucleotides can be prepared in many different forms. Inmost cases, it is desirable to apply the active oligonucleotidetopically to one or more hair producing skin areas on a subject. Forthese applications, a composition that flows, or is spreadable orsprayable is advantageous. Examples of such compositions include, forexample, solutions, suspensions, emulsions, lotions, creams, gels,ointments, liposome preparations, and the like. Preparation of suchpharmaceutical compositions is well-known in the art, and can beutilized for the present invention.

Thus, the oligonucleotide formulations useful in the present inventionwill generally include the oligonucleotide(s) and a pharmaceuticallyacceptable carrier, e.g., any liquid or nonliquid carrier, gel, cream,ointment, lotion, paste, emulsifier, solvent, liquid diluent, powder, orthe like, which is stable with respect to all components of the topicalpharmaceutical formulation and which is suitable for topicaladministration of oligonucleotides according to the method of theinvention. Such carriers are well known in the art.

A topical carrier, as noted above, is one which is generally suited totopical drug administration and includes any such materials known in theart. The topical carrier is selected so as to provide the composition inthe desired form, e.g., as a liquid, lotion, cream, paste, gel, orointment, and may be comprised of a material of either naturallyoccurring or synthetic origin. It is essential, clearly, that theselected carrier not adversely affect the oligonucleotide or othercomponents of the topical formulation. Examples of suitable topicalcarriers for use herein include water, alcohols and other nontoxicorganic solvents, glycerin, mineral oil, silicone, petroleum jelly,lanolin, fatty acids, vegetable oils, waxes, and the like. Particularlypreferred formulations herein are colorless, odorless ointments,lotions, creams and gels.

Ointments, which are semisolid preparations, are typically based onpetrolatum or other petroleum derivatives. As will be appreciated by theordinarily skilled artisan, the specific ointment base to be used is onethat provides for optimum oligonucleotide delivery, and, preferably,provides for other desired characteristics as well, e.g., emolliency orthe like. As with other carriers or vehicles, an ointment base should beinert, stable, nonirritating and nonsensitizing. As explained inRemington: The Science and Practice of Pharmacy, 19th Ed. (Easton, Pa.:Mack Publishing Co., 1995), at pages 1399-1404, ointment bases may begrouped in four classes: oleaginous bases; emulsifiable bases; emulsionbases; and water-soluble bases. Oleaginous ointment bases include, forexample, vegetable oils, fats obtained from animals, and semisolidhydrocarbons obtained from petroleum. Emulsifiable ointment bases, alsoknown as absorbent ointment bases, contain little or no water andinclude, for example, hydroxystearin sulfate, anhydrous lanolin andhydrophilic petrolatum. Emulsion ointment bases are either water-in-oil(W/O) emulsions or oil-in-water (O/W) emulsions, and include, forexample, cetyl alcohol, glyceryl monostearate, lanolin and stearic acid.Preferred water-soluble ointment bases are prepared from polyethyleneglycols of varying molecular weight; again, reference may be had toRemington: The Science and Practice of Pharmacy for further information.

Lotions, which are preparations that are to be applied to the skinsurface without friction, are typically liquid or semiliquidpreparations in which solid particles, including the oligonucleotide,are present in a water or alcohol base. Lotions are usually suspensionsof solids, and preferably, for the present purpose, comprise a liquidoily emulsion of the oil-in-water type. Lotions are preferredformulations for oligonucleotide delivery to large body areas, becauseof the ease of applying a more fluid composition. It is generallynecessary that the insoluble matter in a lotion be finely divided.Lotions will typically contain suspending agents to produce betterdispersions as well as compounds useful for localizing and holding theactive agent in contact with the skin, e.g., methylcellulose, sodiumcarboxymethyl-cellulose, or the like.

Creams containing a oligonucleotide for delivery according to the methodof the invention are viscous liquid or semisolid emulsions, eitheroil-in-water or water-in-oil. Cream bases are water-washable, andcontain an oil phase, an emulsifier and an aqueous phase. The oil phase,also sometimes called the “internal” phase, is generally comprised ofpetrolatum and a fatty alcohol such as cetyl or stearyl alcohol; theaqueous phase usually, although not necessarily, exceeds the oil phasein volume, and generally contains a humectant. The emulsifier in a creamformulation, as explained in Remington, supra, is generally a nonionic,anionic, cationic or amphoteric surfactant.

Gel formulations can also be used in connection with the presentinvention. As will be appreciated by those working in the field oftopical drug formulation, gels are semisolid, suspension-type systems.Single-phase gels contain organic macromolecules distributedsubstantially uniformly throughout the carrier liquid, which istypically aqueous, but also, preferably, contain an alcohol and,optionally, an oil.

The oligonucleotide formulations useful in the invention also encompasssprays, that generally provide the oligonucleotide in an aqueoussolution which can be misted onto the skin for delivery. Such spraysinclude those formulated to provide for concentration of theoligonucleotide solution at the site of administration followingdelivery, e.g., the spray solution can be primarily composed of alcoholor other like volatile liquid in which the oligonucleotide can bedissolved. Upon delivery to the skin, the alcohol carrier evaporates,leaving concentrated oligonucleotide at the site of administration.

The oligonucleotide formulations useful in the invention can alsocontain other optional such as opacifiers, anti-oxidants, gellingagents, thickening agents, stabilizers, and the like. Other agents mayalso be added, such as antimicrobial agents, antifungal agents,antibiotics and anti-inflammatory agents such as steroids.

The oligonucleotide formulations can include other components that,while not necessary for delivery of oligonucleotides to the skin, mayenhance such delivery. For example, although it is not necessary to thepractice of the invention, the oligonucleotide formulations may alsocontain a skin permeation enhancer. Suitable enhancers are well know inthe art and include, for example, dimethylsulfoxide (DMSO), dimethylformamide (DMF), N,N-dimethylacetamide (DMA), decylmethylsulfoxide(C.sub.10 MSO), C.sub.2-C.sub.6 alkanediols, and the 1-substitutedazacycloheptan-2-ones, particularly 1-n-dodecylcyclazacycloheptan-2-one(available under the trademark Azone.®; from Whitby ResearchIncorporated, Richmond, Va.), alcohols, and the like. Preferably, theoligonucleotides delivered are substantially free of such permeationenhancers.

The additional components should not substantially interfere with theintegrity or biological activity of the oligonucleotide or theformulation in which it is provided, i.e., the additional components donot adversely affect the uptake of the oligonucleotide by skin cells orchemically modify the oligonucleotide in an undesirable manner.

It will be recognized by those skilled in the art that the optimalquantity and spacing of individual dosages of oligonucleotides will bedetermined by the precise form and components of the oligonucleotideformulation to be delivered, the site of administration, the use towhich the delivery device is applied (e.g., immunization, treatment of acondition, production of transgenic animals, etc.), and the particularsubject to which the oligonucleotide formulation is to be delivered, andthat such optimums can be determined by conventional techniques. It willalso be appreciated by one skilled in the art that the optimal dosingregimen, i.e., the number of doses of oligonucleotides, can beascertained using conventional methods, e.g., course of treatmentdetermination tests. Generally, a dosing regimen will involveadministration of the selected oligonucleotide formulation at least oncedaily, and may be one to four times daily or more.

The practice of the present invention will employ, unless otherwiseindicated, conventional techniques of drug formulation, particularlytopical drug formulation, which are within the skill of the art. Suchtechniques are fully explained in the literature. See Remington: TheScience and Practice of Pharmacy, cited supra, as well as Goodman &Gilman's The Pharmacological Basis of Therapeutics, 9th Ed. (New York:McGraw-Hill, 1996).

Dosage Forms of the Oligonucleotide Formulations

The oligonucleotides can be prepared in unit dosage form (e.g., inampules), or in multidose form. The oligonucleotides may be present insuch forms as suspensions, solutions, gels, or creams, preferably in anaqueous vehicle (e.g., in a buffered solution). Alternatively, theoligonucleotide salt may be in lyophilized form for reconstitution, atthe time of delivery, with a suitable vehicle, such as sterilepyrogen-free water or phosphate-buffered saline (PBS). Both liquid aswell as lyophilized forms that are to be reconstituted preferablycomprise agents, preferably buffers, in amounts necessary to suitablyadjust the pH of the solution. Nonionic materials, such as sugars, arepreferred for adjusting tonicity, and sucrose is particularly preferred.Any of these forms may further comprise suitable formulatory agents,such as starch or sugar, glycerol or saline. The compositions per unitdosage, whether liquid, gel, cream, or solid, may contain from 0.1% to99% of oligonucleotide material.

Delivery Devices

The oligonucleotide formulation can administered using and be providedwithin, a delivery device (e.g., a patch, bandage, etc.) that providesfor both maintenance of contact between the skin of the subject and theoligonucleotide formulation and substantially uninhibited movement ofthe oligonucleotide into the skin. The delivery device generally doesnot in and of itself facilitate movement of the oligonucleotidecontained therein into the skin, but rather primarily acts to ensurethat the oligonucleotide formulation is in contact with the skin for atime sufficient to allow genetic alteration of skin cells. The deliverydevice comprises a delivery means, or “reservoir,” which is saturatedwith a formulation that comprises an amount of oligonucleotidesufficient to genetic alteration of skin cells to which it is to bedelivered and sufficient to elicit the desired biological effect. Forexample, where the delivery device is to be used to deliver aoligonucleotide for genetic immunization of a human, the delivery meansof the device preferably contains an amount of oligonucleotide rangingfrom about 10 .mu.g to about 1,000 .mu.g, preferably from about 100.mu.g to about 500 .mu.g.

Suitable delivery means of the delivery devices of the inventioninclude, but are not limited to, sponges, hydrogels, and absorptivematerials (e.g., gauze) that allow for retention of the oligonucleotideformulation at the site of oligonucleotide administration withoutsubstantially interfering with the delivery of oligonucleotide to theskin. It is important that, upon contact of the delivery means with theskin, the oligonucleotides contained in the delivery means diffuse orotherwise pass from the delivery means into the skin at a rate and in anamount suitable to accomplish the desired effect.

In general, the delivery means has at least two surfaces: a firstsurface that serves as a skin-contacting surface; and a second surfaceopposite the skin-contacting surface. Preferably, the second surface isin contact with a liquid-impermeable coating that substantially preventsmovement of the oligonucleotide out of the delivery means through thesecond surface (e.g., in a direction away from the first skin-contactingsurface). Preferably, the liquid-impermeable coating also decreases therate of dehydration of the oligonucleotide formulation contained in thedelivery means. In one embodiment, the first skin-contacting surface ofthe delivery means is associated with a liquid-impermeable, removablelayer (e.g., release liner), which layer is removed just prior toplacement of the first surface on the skin of a subject foradministration of the oligonucleotide.

The delivery device preferably comprises an adhesive means, which can bea polymeric matrix of a pharmaceutically acceptable contact adhesivematerial, which serves to affix the system to the skin during drugdelivery. The adhesive means facilitates retention of the delivery meanson the skin at the desired site of administration. Preferably, theadhesive means comprises an adhesive substance that allows for retentionof the delivery means at the desired site for a selected amount of time,but additionally allows for easy removal of the delivery means withoutsubstantially adversely affecting the skin with which the adhesivesubstance was in contact.

The adhesive substance used must be biocompatible with the skin of thesubject, and should not substantially interfere with the delivery ofoligonucleotide to the subject. Examples of suitable skin contactadhesive materials include, but are not limited to, polyethylenes,polysiloxanes, polyisobutylenes, polyacrylates, polyurethanes, and thelike. The particular polymeric adhesive selected will depend on theparticular oligonucleotide formulation, vehicle, etc., i.e., theadhesive must be compatible with all components of the oligonucleotideformulation.

In one embodiment, the delivery means and skin contact adhesive arepresent as separate and distinct layers of the delivery device, with theadhesive underlying the delivery means which, in this case, may beeither a polymeric matrix as described above, or it may be a liquid orhydrogel reservoir, or may take some other form. In another embodiment,the delivery means is an adhesive bandage. Exemplary delivery devicessuitable for use in the invention include, but are not limited to, thosedevices described in U.S. Pat. No. 5,160,328; U.S. Pat. No. 5,254,346;U.S. Pat. No. 5,714,162; U.S. Pat. No. 5,667,798; U.S. Pat. No.5,230,896; and U.S. Pat. No. 5,260,066. Methods for preparation ofsuitable delivery means and other elements associated with the deliverymeans, such as an adhesive means are well known in the art.

In another embodiment, the oligonucleotide formulation of the inventionis provided as a patch, wherein the drug composition is containedwithin, for example, a laminated structure that serves as a drugdelivery device to be affixed to the skin. In such a structure, theoligonucleotide composition is contained within a delivery means, or“reservoir,” which lies beneath an upper backing layer. The laminatedstructure may contain a single reservoir, or it may contain multiplereservoirs.

The backing layer in the laminates of the patch, which serves as theupper surface of the delivery device, functions as the primarystructural element of the laminated structure and provides the devicewith much of its flexibility. The material selected for the backingmaterial should be selected so that it is substantially impermeable tooligonucleotide and, preferably, to other components of theoligonucleotide formulation, thus preventing loss of any componentsthrough the upper surface of the device, and preferably substantiallyimpeding dehydration of the composition in the reservoir. The backinglayer may be either occlusive or nonocclusive, depending on whether itis desired that the skin become hydrated during drug delivery. Thebacking is preferably made of a sheet or film of a preferably flexibleelastomeric material. Examples of polymers that are suitable for thebacking layer include polyethylene, polypropylene, polyesters, and thelike.

During storage and prior to use, the laminated structure includes arelease liner. Immediately prior to use, this layer is removed from thedevice to expose the skin-contacting surface of the device, which asnoted above may be either the reservoir itself or a separate contactadhesive layer, so that the system may be affixed to the skin. Therelease liner is preferably made of a material that is substantiallyimpermeable to the oligonucleotide and other components in theoligonucleotide formulation.

Delivery devices suitable for use in the present invention may befabricated using conventional techniques, known in the art, for exampleby casting a fluid admixture of adhesive, oligonucleotide, andcarrier/vehicle onto the backing layer, followed by lamination of therelease liner. Similarly, the adhesive mixture may be cast onto therelease liner, followed by lamination of the backing layer.Alternatively, the oligonucleotide reservoir may be prepared in theabsence of oligonucleotide formulation or excipient, and then loaded by“soaking” in a drug/vehicle mixture.

As with the topical formulations of the invention, the oligonucleotideformulation contained within the delivery means of the delivery devicesmay contain a number of components. Furthermore, such delivery devicescan be used in connection with administration of any of theoligonucleotide formulations described herein, e.g., nakedoligonucleotide formulations, or lipid- or liposome-comprisingoligonucleotide formulations. Regardless of the specific basiccomponents of the oligonucleotide formulation, the oligonucleotideformulation will generally dissolved, dispersed or suspended in asuitable pharmaceutically acceptable vehicle, typically an aqueoussolution or gel. Other components that may be present includepreservatives, stabilizers, and the like.

Packaging of the Oligonucleotide Formulations and Delivery Devices

The units dosage ampules, multidose containers, and/or delivery devices(e.g., patches) in which the oligonucleotides are packaged prior to usemay comprise an hermetically sealed container enclosing an amount ofoligonucleotide or oligonucleotide formulation containing aoligonucleotide suitable for a pharmaceutically effective dose thereof,or multiples of an effective dose. The oligonucleotide is preferablypackaged as a sterile formulation, and the hermetically sealed containeris designed to preserve sterility of the formulation until use. Wherethe oligonucleotides are provided in a patch-style delivery device, thepatches may be contained in a strip of individually separable packagedpatches for ease in dispensing.

The container in which the oligonucleotide formulation and/or deliverydevice is packaged is labeled, and the label bears a notice in the formprescribed by any appropriate governmental agency. For example, wherethe oligonucleotides are to be administered to humans, the packagecomprises a notice that reflects approval by the Food and DrugAdministration under the applicable federal law, of the manufacture,use, or sale of the oligonucleotide material therein for humanadministration. Federal law requires that the use of pharmaceuticalagents in the therapy of humans be approved by an agency of the Federalgovernment. Responsibility for enforcement is the responsibility of theFood and Drug Administration, which issues appropriate regulations forsecuring such approval, detailed in 21 U.S.C. 301-392. Regulation forbiologic material, comprising products made from the tissues of animalsis provided under 42 U.S.C 262. Similar approval is required by mostforeign countries. Regulations vary from country to country, but theindividual procedures are well known to those in the art.

Introduction of Oligonucleotides into Skin Cells According to the Methodof the Invention

Application of the Oligonucleotide to Skin

Administration of the oligonucleotide is accomplished by contacting aoligonucleotide-comprising formulation (e.g., a buffered salt solutioncomprising the oligonucleotide) with an area of skin for a timesufficient to allow genetic alteration of skin cells. Preferably, theoligonucleotide is applied to hirsute skin. The oligonucleotide can beapplied to skin without substantial pretreatment or with pretreatment,preferably without pretreatment of the skin. “Pretreatment” cangenerally encompass removal of hair from the skin, increasing skinpermeability by mechanical means (e.g, abrasion), increasing skinpermeability by application of a chemical agent to the site eitherbefore or during oligonucleotide administration, and application of anirritant or other like chemical agent to elicit a non-specific immuneresponse or an immune response toward the irritant (e.g., by applicationof a keratinolytic agent). Administration of the oligonucleotide can beaccomplished according to the invention without the application of anelectric field or electric pulse (e.g., as in iontophoresis), withoutbreaking the skin (e.g., by abrasion or through use of a needle), andwithout application of pressure to the site of administration (e.g., viajet propulsion, pressurized air, etc.). Furthermore, oligonucleotideadministration can be accomplished using a oligonucleotide formulationthat is substantially free of permeabilizing agents, detergents, orother chemical agents that facilitate entry of the oligonucleotide intothe skin.

Once the oligonucleotide-comprising formulation is brought into contactwith skin, contact is maintained for a time sufficient to allow movementof the oligonucleotide from the formulation into skin and into skincells. In general, the time of contact between the oligonucleotide andthe skin will be at least about 1 min to about 1 hr or more, preferablyat least about 30 min. Because there is substantially no toxicityassociated with contacting the oligonucleotide with the skin, the timeof contact maintained between the oligonucleotide and the skin to whichthe oligonucleotide is to be delivered is limited only by such factorsas the ability to keep the oligonucleotide in a suitable delivery form(e.g., a time during which the oligonucleotide-comprising solution canbe prevented from dehydrating) and the ability to physically maintaincontact between the oligonucleotide and the site of delivery (e.g.,maintenance of a patch comprising the oligonucleotide(s) on the skin).Therefore, the time of contact of a single dose can be as long asseveral hours to several days, and may be weeks or more. Furthermore,the time of delivery can be further extended by additional subsequentapplications of the oligonucleotide to the same or different deliverysite on the skin.

While an ethanolic/propylene glycol solution of anti-hairlessoligonucleotide as found to deliver beneficial amounts ofoligonucleotide to the hair follicle and result in inhibition ofhairless, other formulations can also advantageously be used. Inparticular, liposome compositions can be advantageous. Liposomes wereintroduced first in about 1980 for topical drug delivery and have sinceattracted considerable interest due to their potential utility both as adrug carrier and a reservoir for controlled release of drugs withinvarious layers of the skin and the hair follicle. In addition toreducing the undesirable high systemic absorption of topically applieddrugs, the major advantage of liposomes compared to other formulationssuch as ointments or creams, is based on their ability to create adepot, from which the drug is slowly released. The delivery agents alsoprovide advantages in that they protect oligonucleotides againstdegradation, increase cellular uptake, and may target the drug tospecific cells or tissue compartment. Thus, a delivery system allowingthe controlled and sustained release of oligonucleotides in vivo cangreatly increase the efficacy of gene inhibition technology.

One of the most favored sites of liposome penetration is into the hairfollicle, since the hair canal opens directly onto the surface of theskin. Liposomes applied to cultured hair follicles are easily detectedin cells lining the inner root sheath. (Li et al., 1992b, In Vitro CellDev Biol 28A:679-681.) Liposomes also find their way into thepilosebaceous unit once traveling down the root sheath. (Lieb et al.1992, J Invest Dermatol 99:108-113.) Liposomes have been shown to directcompounds into the sebaceous gland, when they would otherwise be trappedin the stratum corneum. (Bernard et al., 1997, J Pharm Sci 86:573-578.)Liposomes function both as a controlled release system and as a deliverysystem transporting encapsulated substances into cells. After topicalapplication, and upon drying, the liposomes develop into a structuredfilm that fills the follicular openings, intimately mixing with thefollicular contents, and fostering drug diffusion to the depths of thefollicles.

A number of different compositions of liposomes have been tested for invivo oligonucleotide delivery. For example, three different lipids werecompared: N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl ammoniumchloride (DOTMA), 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminium trifluoroacetate (DOSPA) andN-(1-(2,3-dimyristyloxypropyl)-N,N dimethyl-(2-hydroxyethyl) ammoniumbromide (DMRIE). The macrophages incorporated tenfold moreoligonucleotide when delivered in conjunction with DOSPA than with theother cationic lipids.

Liposome preparation and encapsulation of oligonucleotides are availablefrom commercial manufacturer, e.g., BioZone Laboratories, Inc.Pittsburg, Calif., which manufactures a wide range of topically appliedLipoCeutical products that include cationic lipids.

In addition to cationic lipid liposomes, other types of liposomes canalso be used, e.g. pH-sensitive liposomes. The cellular uptake ofliposomes passes mainly through an endocytic pathway, and occasionally,liposomes and their contents inadvertently arrive in the lysosomes wherethey are degraded. The quantity of oligonucleotides that can avoiddegradation and reach their nuclear or cytoplasmic target is probablyvery low. To overcome lysosomal degradation and in order to increase theefficiency of delivery, pH sensitive fusogenic liposomes have been used.These consist of a non-bilayer-forming lipid such asdioleylphosphatidylethanolamine (DOPE) and a titratable acidicamphiphile such as oleic acid (OA) or cholesterylhemisuccinate (CHEMS).(DeOliveira et al., 1998, Biochim. Biophys. Acta Biomembr.1372:301-310.) At pH 7, the amphiphile maintains the lipid mix in abilayer (liposome) structure. However, as the complex moves through theendosomes, the pH drops and the amphiphile becomes protonated. Thiscauses the liposome to collapse resulting in fusion with the endosomalmembrane and release of the liposome contents into the cytoplasm.However, the anionic nature of pH-sensitive liposomes may lead to poorencapsulation of ODNs. (Hughes et al., 2000, Methods Enzymol313:342-358.).

As one alternative to liposomes, other carriers/delivery agents can beused, such as cationic polymers. The most widely studied polymers arepolylactides and co-polymers of lactic acid and glycolic acid P(LA-GA)and both of these have been evaluated for the use for delivery ofoligonucleotides. (Lewis et al., 1998, J Drug Target 5:291-302; Hudsonet al., 1999, Int J Pharm 182:49-58.)

In addition to the above, certain patents have described methods fordelivery that can be used in the present invention. Examples include thefollowing.

Li and Lishko, U.S. Pat. No. 5,914,126 (incorporated herein by referencein its entirety) describes methods to deliver macromolecules to hairfollicles, where the method involves applying to the skin a formulationthat includes a macromolecule, such as a nucleic acid, in a liposomalformulation, such that the liposomes target the macromoleculeselectively into hair follicle cells by transfer into the folliclewithout entry into the circulation of the adjacent skin tissue.

Khavari et al., U.S. Pat. No. 6,087,341 (incorporated herein byreference in its entirety) describes methods and compositions forintroduction of nucleic acid into skin cells by topical application.

Li and Baranov, U.S. Pat. No. 6,080,127 (incorporated herein byreference in its entirety) describes a skin vibration method for topicaltargeted delivery of beneficial agents into hair follicles. Thevibration frequency can, for example, be about 1 Hz to 100 Hz.

In some applications, it may be useful to include transdermalpenetration enhancers, for example, as described in Karande et al.,2004, Nature Biotech. 192-197. As described, two types of compositionswere particularly effective. One included sodium laureth sulfate (SLA)with phenyl piperazine (PP). In a particular composition the SLA:PP wasas 0.5% (w/v) with the weight ration of SLA=0.7 in the combination.

The second included N-lauroyl sarcosine (NLS) with sorbitan monolaurate(S20). In a particular composition, the combination was at 1.0% (w/v)with the weight ration of NLS=0.6.

G. Administration

The present compositions can be administered in various ways, e.g.,depending on the condition to be treated, and the type of composition tobe used. In many cases, topical administration will be used. This modeof administration is particularly suitable for local hair removal.

In some applications, hair removal is desired in only a portion of theskin area of a subject. In those cases, the composition can be appliedlocally.

Exemplary Topical Application Methods

Spreading

In most cases, the composition containing the RNAi inducingoligonucleotides will be spread or wiped on the treatment area to form athin film. Thus, for example, for any of the forms of liquid suspensionor solution, cream, lotion, gel, or ointment, a quantity of thecomposition is spread on the treatment surface or surfaces of thesubject, and left for a time to allow oligonucleotides (which may be ina carrier species such as in liposomes, to migrate to the hairfollicles.

Spraying

For compositions that are sufficiently liquid, the composition can besprayed on the treatment site, either with or without protection againstoverspray on surrounding areas. For spray applications, it may bedesirable to protect against inhalation of sprayed material, e.g., byusing masks that will filter out the relevant sized aerosol particles.

Injection

In some applications, it will be desirable to remove only specifichairs. Thus, rather than contacting a particular area, a compositionwill be delivered to one or more particular hair follicles. Suchindividual follicle delivery can be accomplished in various ways. Forexample, a drop of liquid containing the active oligonucleotide(s) canbe deposited on the hair shaft, and allowed to migrate down the shaft tothe follicle. In another approach, a needle can be inserted in the hairchannel, and liquid or other composition deposited at or near thefollicle.

Application Site Preparation and Hair Cycle Synchronization

In some cases, the present compositions can be applied without anyspecial preparation of the application site. In other cases, however, itis advantageous to prepare the site, e.g., by preliminary removal ofhair from the site and/or to combine the present invention with asupplementary method of hair removal. Such removal can be beneficial inseveral different ways. For example, such removal can reduce the amountof active agent required for the present invention because the materialwill not be lost by adhering to the hair, and instead will be availablefor absorption/migration to the hair follicles.

Such removal can also be beneficially be used to supplement the presentinvention by removing residual hairs. Depending on the manner and amountof RNAi inducing oligonucleotide delivered to the hair follicles, someof the follicles may not be sufficiently inhibited, such that some hairsmay grow in the treated area and/or some hairs may be reduced inthickness or length but still present. In such cases, a supplementarymethod of hair removal can be used to produce a desired level of hairremoval, e.g., shaving, chemical depilation, enzymatic hair removal;laser treatment; electrolysis. Certain embodiments of the presentinvention include such an supplemental method.

It can also be advantageous to synchronize hair cycles in the treatmentarea. Such synchronization can advantageously be done prior toapplication of the present compositions, or during an interval oftreatment with the present compositions, or in an interval between twooccasions or intervals of application of the present compositions.

Such synchronization can be accomplished, for example, by pulling hairsfrom the follicles (either individually or in larger numbers). Examplesof methods for pulling the hairs include plucking and waxing. In somecircumstances it will be necessary/desirable to induce folliclesynchrony by molecular means. In these instances, skin is treated with aknown follicle growth inducer such as cyclosporin A, TPA, Noggin,estrogen receptor agonist, and the like.

In general, if a hair is pulled from a follicle in anagen, that folliclegoes into catagen; if a hair is pulled from a follicle in telogen, thefollicle is stimulated to produce hair, and thus goes into anagen. Thus,for a more extensive effect using the present invention, a distributionof hairs in anagen, catagen, and telogen can be synchronized in catagen,with one pulling to push anagen follicles to catagen, and two pullingsto stimulate telegen follicles to anagen, and then push the newly anagenfollicles to catagen. Depending on the reaction of the follicles, suchprocedure can produce a single phase synchrony, or a two phasesynchrony.

EXAMPLE 1 In vitro siRNA Inhibition of Hairless mRNA

siRNAs were commercially obtained from Ambion, Inc. for human and mousehairless genes. These are validated, chemically synthesized siRNAs, thatare HPLC purified, annealed and ready to use, and guaranteed to reducetarget gene expression by 70% or more. For both human and mousetranscripts, two different siRNAs were used. The sequence of thehairless siRNAs is given in the following table. In this and thesubsequent tables in this example, upper case letter are used to referto the human homologs, and lower case letter refer to the mouse homologsof the specified genes.

List of Pre-Designed siRNAs Used for Gene Silencing Experiments. siRNASense Sequence Antisense Sequence HR#1 5′-GGACAUGCUCCCACUUGUGtt-3′5′-CACAAGUGGGAGCAUGUCCtt-3′ (SEQ ID NO: 11355) (SEQ ID NO: 11356) HR#25′-GGAGGCCAUGCUUACCCAUtt-3′ 5′-AUGGGUAAGCAUGGCCUCCtt-3′ (SEQ ID NO:11357) (SEQ ID NO: 11358) hr#1 5′-GGACACACUCUCACUGGUGtt-3′5′-CACCAGUGAGAGUGUGUCCtt-3′ (SEQ ID NO: 11359) (SEQ ID NO: 11360) hr#25′-GGGCUUUUACCACAAGGAUtt-3′ 5′-AUCCUUGUGGUAAAAGCCCtt-3′ (SEQ ID NO:11361) (SEQ ID NO: 11362)

We also used siRNAs for the mouse glyceraldehyde-3-phosphatedehydrogenase (gapdh) gene, Silencer™ GAPDH siRNA (Cat no. 4605, Ambion,Inc. Austin, Tex.) as controls to monitor and optimize siRNAexperiments.

Human HaCaT, HeLa and mouse NIH 3T3 cells were used in siRNAtransfection experiments. Cells were plated on 6-well tissue cultureplates in Dulbecco's Modified Eagle Media (D-MEM, Cat no. 10569-010,Invitrogen Corp., Carlsbad, Calif.) with 10% Fetal Bovine Serum (Cat no.16000-044, Invitrogen, Corp.) so that they were 30-50% confluent at thetime of transfection. Immediately before the transfection, the cellswere washed in Opti-MEM I Reduced Serum Medium (Cat no. 31985-070,Invitrogen, Inc.). We used 200 μmol of short interfering RNA (siRNA) foreach well and the Oligofectamine™ reagent. The transfections wereperformed according to the manufacturer's instructions (Cat no.12252-011, Invitrogen, Inc).

Total RNA was isolated 24 and 48 hours post-transfection using theRNeasy Mini Kit (Cat no. 74104, QIAGEN, Inc., Valencia, Calif.)according to the manufacturer's instructions. cDNA synthesis wasperformed using the SuperScript First-Strand Synthesis System for RT-PCRkit (Cat no. 11904-018, Invitrogen, Corp.) and oligo (dT) primers. Geneactivity was determined by the Real-Time quantitative RT-PCR (qRT-PCR)technique.

Real Time Quantitative RT-PCR (qRT-PCR)

Real-Time qRT-PCR was performed using MJ Research Opticon 2 continuousfluorescence detector. For qRT-PCR 40 ng of cDNA obtained from culturedHaCaT, HeLa, and NIH3T3 cells (siRNA treated and untreated), wasamplified using the MJ Research DyNAmo Hot Start SYBR Green qPCR kit(Cat no. F-410L, MJ Research, Inc., Waltham, Mass. The DyNAmo Hot StartSYBR Green qPCR kit is a master mix of a modified hot start DNApolymerase with SYBR Green I and the appropriate buffers, all of whichhave been optimized for real-time quantitative analysis with the MJResearch Opticon 2. PCR amplification of cDNA samples was performed in96 well optical plates under the following conditions: 1. Incubate at95.0 C. tor 00:10:00 2. Incubate at 95.0 C. for 00:00:20 3. Incubate at55.0 C. for 00:00:30 4. Incubate at 72.0 C. for 00:00:40 5. Plate Read6. Incubate at 77.0 C. for 00:00:01 7. Plate Read 8. Go to line 3 for 39more times 9. Incubate at 72.0 C. for 00:05:00 10. Melting Curve from65.0 C. to 95.0 C. read every 0.2 C. hold 00:00:01 11. Incubate at 72.0C. for 00:05:00 END

The list of PCR primers used for Real Time PCR amplifications is givenin the following table.

PCR primers used for Real-Time RT-PCR amplifications of mouse and humanhairless, mouse glyceraldehyde-3-phosphate dehydrogenase gene, andhypoxanthine guanine phosphoriboxyltransferase 1 (hprt). (HPRT was usedas a normalizing internal control in mouse cells the same way GAPDH wasused for the human cell lines.) Gene Forward primer Reverse primer Hr5′-TTCTACCGCGGTCAAACTCT-3′ 5′-TTGGTGTCAGGGATCCAAAG-3′ (SEQ ID NO: 11363)(SEQ ID NO: 11364) GAPDH 5′-AGCCACATCGCTCAGAACAC-3′5′-GAGGCATTGCTGATGATCTTG-3′ (SEQ ID NO: 11365) (SEQ ID NO: 11366) hr5′-ACATCAAAGAAGAGACCCCAG-3′ 5′-TTCGCACTGGTGACAATGGAA-3′ (SEQ ID NO:11367) (SEQ ID NO: 11368) gapdh 5′-GTGAACGGATTTGGCCGTATT-3′5′-TTTTGGCTCCACCCTTCAAGT-3′ (SEQ ID NO: 11369) (SEQ ID NO: 11370) hplt5′-CCCTGGTTAAGCAGTACAGC-3′ 5′-CAGGACTAGAACACCTGCTAA-3′ (SEQ ID NO:11371) (SEQ ID NO: 11372)

Plate readings for fluorescence levels are taken at two steps, 5 and 7.These values indicate the relative amounts of amplicon per well at aparticular cycle. The raw numbers obtained from these readings were usedto determine the PCR amplification efficiency. This is the measurementof fold amplification per PCR cycle, and is expressed as a fraction orpercentage relative to perfect doubling. A PCR resulting in perfectdoubling would exhibit 100% amplification efficiency. All of thecalculations are done using the LinRegPCR program by J. M. Ruijter andC. Ramakers. The crossing threshold for the experiment is determinedmanually and is defined at the cycle at which amplification for allsamples becomes logarithmic. The relative fold for each amplicon is thendetermined using the amplification efficiency and crossing threshold forthat particular amplicon and normalizing it against the relativestarting amounts, which is determined by the GAPDH amplificationefficiency and crossing threshold that corresponds to that sample. Thisis done using parameters and equations set by Lui and Saint (AnalyticalBiochemistry 302, 52-59 (2002)). The final values can then be used tocompare the fold differences in gene expression of a particular geneacross several different samples or conditions.

This technique and analysis can be applied to determine the levels ofhairless expression, or more specifically, the efficiency of genesilencing using hairless siRNA through comparison of the treated anduntreated cell populations.

The following table shows the percentage of gene silencing observedfollowing siRNA treatment of human HeLa and HaCaT cells. Total RNA wascollected 48 hours following transfection with siRNAs for hairless (Hr)gene. Gene activity was assayed by real-time quantitative RT-PCR(qRT-PCR) technique. Percent knockdown is calculated by obtaining theratio of the normalized level of Hr expression in treated and untreatedcell populations and subtracting this value from 1 (100% expression).Gene Expression Cell Percent RNA isolation siRNA Tested Type Knockdowntime point HR#1 Hr HeLa 97.3% 48 hours HR#2 Hr HeLa 98.7% 48 hours HR#2Hr HaCaT 95.8% 48 hours

The following table shows the percentage of gene silencing observedfollowing siRNA treatment of mouse NIH3T3 cells. Total RNA was collected48 hours following transfection with siRNAs for hairless (hr) andglyceraldehyde-3-phosphate dehydrogenase (gpdh) genes. Gene activity wasassayed by real-time quantitative RT-PCR (qRT-PCR) technique. Percentknockdown is calculated by obtaining the ratio of the normalized levelof hr and gapdh expression in treated and untreated cell populations andsubtracting this value from 1 (100% expression). Gene Expression CellPercent RNA isolation siRNA Tested Type Knockdown time point hr#1 HrNIH3T3 99.3% 48 hours hr#2 Hr NIH3T3 99.17% 48 hours Gapdh Gapdh NIH3T399.3% 48 hours

EXAMPLE 2 In Vivo Testing: A Phase 1 Clinical Trial of Anti-HairlesssiRNA

The goal of this study is to establish the safety of topical applicationof anti-hairless siRNA (Trichozyme) in healthy human subjects at a doseof 10 μg daily, administered over a period of 3 months.

Inhibition of gene expression using or siRNA technology is a recentlydeveloping area of therapy. Several recent studies indicate theusefulness of such therapeutic strategies in a number of differentconditions. Our preliminary in vivo studies demonstrated the inhibitionof hairless mRNA can be used to permanently inhibit hair growth inexperimental animals. Briefly, they inhibit translation from the mRNAtranscript originating from the human hairless gene, the first knowngene participating in the regulation of the human hair cycle asidentified by our group earlier, preventing the synthesis of functionalhairless protein. Presence of hairless protein is necessary foruninterrupted hair cycling, and lack of hairless gene expression due toa deleterious mutation or temporary inhibition leads to a permanentinhibition of hair growth and the involution of hair follicles asevidenced by our own in vivo trials in animal models. The successfultranslation of the result of animal studies to human application leadsto a strategy to obtain permanent inhibition of hair growth by temporarytopical treatment with Trichozyme.

Study Design

This will be an open label, uncontrolled, safety study. Monitoring forside effects, alterations in hematology, serum chemistries and urineanalysis will continue during the 3 month treatment period as well asduring the 6 month follow up period after the application is stopped.Subjects will be seen daily by Study personnel during the treatmentperiod and monthly during the follow-up period. The Study will not offertreatment of any side effects that develop.

We will enlist 20 subjects, 10 of which will be treated with the siRNAin an isopropranol or liposomal based vehicle, the other 10 subject willreceive treatment with vehicle only. Hair from the dorsal surface of theleft forearm will be removed by waxing before applying treatment duringthe first 30 days of the study. Treatment will consist of topicalapplication of an isopropranol based solution alone or containinganti-hairless siRNA over a 15 cm² area of the dorsal surface of the leftforearm using a glass rod. Ample time will be left for absorption.

Subjective side effects, alterations in serum chemistry, hematology andurine analysis will be monitored as well as serum and urine isopropranollevel and presence of Trichozymes in serum and urine samples.Photography of the treatment area and hair count will be performedduring the initial visit and weekly afterwards during the treatmentperiod of the study then monthly during the follow-up period of thestudy.

Study Procedures

Before entering in the study subjects will sign an informed consent fordisclosure of medical records. A screening questionnaire will becompleted as well as a review of medical records to exclude anypreexisting medical conditions affecting hair growth or otherpreexisting diseases listed as exclusion criteria.

Laboratory evaluation—Fasting blood and urine samples will be obtainedfor the following tests: (a) Hematology—hemoglobin and hematocrit, CBCwith differential and platelet count, (b) Serum Chemistry—sodium, totalbilirubin, potassium, glucose, chloride, alkaline phosphatase, calcium,AST, ALT, inorganic phosphorus, BUN, creatinine, bicarbonate; (c)urinalysis—protein, glucose, pH, Ketones, nitrates, blood (d.) pregnancytest.

Screening/Baseline Visit—Informed consent for study participationsigned. Complete history (including record of systemic and topicalmedication, both prescription and non-prescription). Physicalexam—Comprehensive skin exam and photography of the treatment area andhair count. (e) Review criteria for inclusion/exclusion and determineeligibility.

Daily Clinic Visits for treatment—waxing of the treatment area (forfirst 30 days only) followed by topical application of Treatment. Bloodand urine samples for Hematology, Serum chemistry, Urine analysis,Isporopranol serum/urine level and siRNA detection in serum/urine willbe obtained monthly. Photography of the treatment area and hair countwill be performed weekly. Subjects will be interviewed for subjectiveside effects weekly.

Monthly Clinic Visits for follow-up—Blood and urine samples forHematology, Serum chemistry, Urine analysis, Isporopranol serum/urinelevel and siRNA detection in serum/urine will be obtained. Photographyof the treatment area and hair count. Subjects will be interviewed forsubjective side effects.

Study Site—Subjects will be seen at the clinical facilities for thestudy.

Study Drugs

siRNAs for the study are are oligonucleotides with RNAi activity that isspecific to mRNA sequences present in the human hairless mRNA. Thisstudy will utilize a mixture of 8-10 different siRNAs. To date there isno data available of topical cutaneous application of anydeoxy-ribozymes. The siRNAs to be used in this study will be provided bya manufacturer offering custom synthesized human grade oligonucleotides.

Study Questionnaires

All subjects will complete study questionnaires at baseline.

Study Subjects

Criteria—Inclusion—(i) Study subjects must be 18 to 35 years of age,female of Hispanic ethnicity. (ii) Have no previous medical history ofhair growth abnormalities or endocrine, renal, autoimmune, cardiac,pulmonary, hematological or psychiatric disorders. (iii) Other inclusioncriteria: (iv) The subject has provided written informed consent priorto administration of any study-related procedures. (v) The subject hasbeen using adequate contraception since her last menses and will useadequate contraception during the study, is not lactating, and has adocumented negative serum pregnancy test within 14 days prior to thefirst dose of study medication. (vi) The subject is willing to abstainfrom any voluntary alteration of body hair of the treated area. (vii)The subject is willing to abstain from application of prescription andover the counter topical medications for the duration of the study,including moisturizers, emollients and sunscreens. (viii) The subject iswilling to return for scheduled follow-up visits for the duration of thestudy. (ix) The subject must meet the following laboratory criteriaduring a time not to exceed 8 weeks prior to randomization: 1)hemoglobin level of greater than 12.0 (women) or 13.0 (men); 2) WBCcount greater than 3000/mm³; 3) platelet count greater than 125,000; 4)BUN within normal limits; 5) electrolytes within normal limits; 6)creatinine≦1.5×ULN; 7) AST≦1.5×ULN; 8) ALT≦1.5×ULN; 9) total bilirubinwithin normal limits; and 10) creatinin clearance within normal limits.

Exclusion—(i) existence of any medical conditions listed above. (ii) anylaboratory values that do not meet the criteria listed above. (iii)Pregnancy or lactation. (iv) Invasive cancer or anticipated hormonal,chemo-, or radiotherapy while participating in the study. (v) Anymedical or psychosocial condition that, in the opinion of theinvestigator, could jeopardize subject's participation in this study.

Recruitment of Subjects

Potential subjects for this Study will be recruited from among residentsin proximity to the study site because of the daily visit requirements.Subjects with Hispanic ethnicity will be recruited to avoidinter-ethnicity variations of hair density and follicle site as well asblonde hair that is less appropriate for complete hair count andphotography.

EXAMPLE 3 Hair Removal Using In Vivo Knockdown of Hairless mRNA

It was demonstrated that inhibiting the expression of hairless mRNA inan animal model system created essentially a hairless condition. Thisexemplary test was conducted using ribozymes targeting the hairlessmRNA, and is described in Cserhalmi-Friedman et al., Exp Dermatol., 2004March; 13(3):155-62, which is incorporated herein by reference in itsentirety.

Short Term Results in Newborn Mice

The mice, who were gender-matched littermates, were sacrificed afterfour weeks of treatment that started immediately after the animals wereborn. All treated mice demonstrated a variable degree of visiblesparseness of hair at the treated area of the back, which was notobserved in the control animals treated with nonspecific deoxyribozymes.The specimens taken from the control animal show the presence of largenumber of hair follicles in anagen V stage, corresponding to theclinical appearance. In contrast, the samples taken from the treatedmice demonstrate the presence of smaller hair follicles withmorphological features similar to those observed in anagen III stage(i.e.: hair shaft did not reach the level of the sebaceous gland). Alarge portion of the hair follicles in the treated region showed delayedanagen development as well as significant dilatation of the hair canal,reminiscent of utricles characteristic of the hairless phenotype. Inthese samples, we observed several large cysts filled with keratinousmaterial and remnants of coiled and degraded hair follicles. Thesedermal cysts are believed to be the result of hair follicledisintegration and abnormal hair shaft formation. Importantly, dermalcysts are hallmark features of the hairless phenotype and usuallycontain either keratinous mass or a degraded hair shaft, as seen in thesample taken from the skin of a hairless mouse. The inhibition of hairgrowth, formation of the utriculi, and appearance of dermal cysts werepresent in all treated mice, but were not detected in any controlanimals.

b. Long Term Results in Newborn Mice

Another group of littermates of identical gender was sacrificed afterseven weeks of treatment that started immediately after the animals wereborn. A noticeable decrease in the density of hair was present in thetreated animals as compared to the control mice treated with onspecificdeoxyribozymes. The sample from the control animals showed the presenceof regularly spaced telogen hair follicles. In the treated area, weobserved a significantly decreased number of follicles with large areasof the skin devoid of any hair follicles at all. In the treated area, wedetected the presence of large cysts filled with amorphous keratinmaterial, corresponding to dermal cysts, which are characteristics ofthe hairless phenotype. Histopathology of the treated area showed thepresence of small dense groups of cells with condensed nuclei in thedeep dermis. These cell groups were reminiscent of detached dermalpapillae, which are typically found in hairless mice. The lack of hairfollicles, the presence of dermal cysts and the detached dermal papillaewere present in every treated animal, while all the control animalsshowed the presence of evenly spaced telogen follicles.

c. Results in Depilated Animals

This group of eight week old female littermates was wax-depilated andsubsequently sacrificed after four weeks of treatment that beganimmediately after the depilation. Clinically, the control animals showedactive hair regrowth in the depilated area.

In contrast, the hair regrowth was of lesser magnitude in the treatedmice, and the hair became sparse (not shown). Histopathology of thecontrol mouse skin shows the presence of a large number of hairfollicles in advanced anagen. In the samples taken from the treatedanimals, the treated regions could be easily identified by the lack ofdepilation-induced hair regrowth. These untreated hair follicles wereidentical to those observed in the control animals treated withnonspecific deoxyribozymes. On histology, the treated area with smalltelogen hair follicles could be easily distinguished from neighboringuntreated area with hair follicles at advanced anagen stages, suggestingthat in the treated portion of skin the hair follicles were not able toenter depilation-induced anagen at all, or exhibited much lower growthrates compare to control skin.

All patents and other references cited in the specification areindicative of the level of skill of those skilled in the art to whichthe invention pertains, and are incorporated by reference in theirentireties, including any tables and figures, to the same extent as ifeach reference had been incorporated by reference in its entiretyindividually.

One skilled in the art would readily appreciate that the presentinvention is well adapted to obtain the ends and advantages mentioned,as well as those inherent therein. The methods, variances, andcompositions described herein as presently representative of preferredembodiments are exemplary and are not intended as limitations on thescope of the invention. Changes therein and other uses will occur tothose skilled in the art, which are encompassed within the spirit of theinvention, are defined by the scope of the claims.

It will be readily apparent to one skilled in the art that varyingsubstitutions and modifications may be made to the invention disclosedherein without departing from the scope and spirit of the invention. Forexample, variations can be made to the number, length, and chemicalmodifications in the dsRNA. Thus, such additional embodiments are withinthe scope of the present invention and the following claims.

The invention illustratively described herein suitably may be practicedin the absence of any element or elements, limitation or limitationswhich is not specifically disclosed herein. Thus, for example, in eachinstance herein any of the terms “comprising”, “consisting essentiallyof” and “consisting of” may be replaced with either of the other twoterms. The terms and expressions which have been employed are used asterms of description and not of limitation, and there is no intentionthat in the use of such terms and expressions of excluding anyequivalents of the features shown and described or portions thereof, butit is recognized that various modifications are possible within thescope of the invention claimed. Thus, it should be understood thatalthough the present invention has been specifically disclosed bypreferred embodiments and optional features, modification and variationof the concepts herein disclosed may be resorted to by those skilled inthe art, and that such modifications and variations are considered to bewithin the scope of this invention as defined by the appended claims.

In addition, where features or aspects of the invention are described interms of Markush groups or other grouping of alternatives, those skilledin the art will recognize that the invention is also thereby describedin terms of any individual member or subgroup of members of the Markushgroup or other group.

Also, unless indicated to the contrary, where various numerical valuesare provided for embodiments, additional embodiments are described bytaking any 2 different values as the endpoints of a range. Such rangesare also within the scope of the described invention.

Thus, additional embodiments are within the scope of the invention andwithin the following claims. TABLE 1 cDNA Human Hairless 19-mer TargetSequences and Complement Referenced to NM_005144- Homo sapiens hairlesshomolog (mouse) (HR), transcript variant 1, complete mRNA (1-5699 bp).(SEQ ID NO: for Sense equals (2X − 1) SEQ ID NO: for Antisense equals(2X), (e.g. where X = 1 Sense has SEQ ID NO: 1 and Antisense has SEQ IDNO: 2) X Sense (5′-3′) Antisense (5′-3′) 1 TCTCCCGGGAGCCACTCCCGGGAGTGGCTCCCGGGAGA 2 CTCCCGGGAGCCACTCCCA TGGGAGTGGCTCCCGGGAG 3TCCCGGGAGCCACTCCCAT ATGGGAGTGGCTCCCGGGA 4 CCCGGGAGCCACTCCCATGCATGGGAGTGGCTCCCGGG 5 CCGGGAGCCACTCCCATGG CCATGGGAGTGGCTCCCGG 6CGGGAGCCACTCCCATGGG CCCATGGGAGTGGCTCCCG 7 GGGAGCCACTCCCATGGGCGCCCATGGGAGTGGCTCCC 8 GGAGCCACTCCCATGGGCG CGCCCATGGGAGTGGCTCC 9GAGCCACTCCCATGGGCGC GCGCCCATGGGAGTGGCTC 10 AGCCACTCCCATGGGCGCCGGCGCCCATGGGAGTGGCT 11 GCCACTCCCATGGGCGCCT AGGCGCCCATGGGAGTGGC 12CCACTCCCATGGGCGCCTC GAGGCGCCCATGGGAGTGG 13 CACTCCCATGGGCGCCTCTAGAGGCGCCCATGGGAGTG 14 ACTCCCATGGGCGCCTCTC GAGAGGCGCCCATGGGAGT 15CTCCCATGGGCGCCTCTCC GGAGAGGCGCCCATGGGAG 16 TCCCATGGGCGCCTCTCCATGGAGAGGCGCCCATGGGA 17 CCCATGGGCGCCTCTCCAG CTGGAGAGGCGCCCATGGG 18CCATGGGCGCCTCTCCAGC GCTGGAGAGGCGCCCATGG 19 CATGGGCGCCTCTCCAGCCGGCTGGAGAGGCGCCCATG 20 ATGGGCGCCTCTCCAGCCC GGGCTGGAGAGGCGCCGAT 21TGGGCGCCTCTCCAGCCCC GGGGCTGGAGAGGCGCCCA 22 GGGCGCCTCTCCAGCCCCTAGGGGCTGGAGAGGCGCCC 23 GGCGCCTCTCCAGCCCCTG CAGGGGCTGGAGAGGCGCC 24GCGCCTCTCCAGCCCCTGG CCAGGGGCTGGAGAGGCGC 25 CGCCTCTCCAGCCCCTGGCGCCAGGGGCTGGAGAGGCG 26 GCCTCTCCAGCCCCTGGCC GGCCAGGGGCTGGAGAGGC 27CCTCTCCAGCCCCTGGCCT AGGCCAGGGGCTGGAGAGG 28 CTCTCCAGCCCCTGGCCTGCAGGCCAGGGGCTGGAGAG 29 TCTCCAGCCCCTGGCCTGG CCAGGCCAGGGGCTGGAGA 30CTCCAGCCCCTGGCCTGGA TCCAGGCCAGGGGCTGGAG 31 TCCAGCCCCTGGCCTGGAATTCCAGGCCAGGGGCTGGA 32 CCAGCCCCTGGCCTGGAAG CTTCCAGGCCAGGGGCTGG 33CAGCCCCTGGCCTGGAAGC GCTTCCAGGCCAGGGGCTG 34 AGCCCCTGGCCTGGAAGCATGCTTCCAGGCCAGGGGCT 35 GCCCCTGGCCTGGAAGCAC GTGCTTCCAGGCCAGGGGC 36CCCCTGGCCTGGAAGCACC GGTGCTTCCAGGCCAGGGG 37 CCCTGGCCTGGAAGCACCATGGTGCTTCCAGGCCAGGG 38 CCTGGCCTGGAAGCACCAG CTGGTGCTTCCAGGCCAGG 39CTGGCCTGGAAGCACCAGG CCTGGTGCTTCCAGGCCAG 40 TGGCCTGGAAGCACCAGGATCCTGGTGCTTCCAGGCCA 41 GGCCTGGAAGCACCAGGAA TTCCTGGTGCTTCCAGGCC 42GCCTGGAAGCACCAGGAAC GTTCCTGGTGCTTCCAGGC 43 CCTGGAAGCACCAGGAACCGGTTCCTGGTGCTTCCAGG 44 CTGGAAGCACCAGGAACCC GGGTTCCTGGTGCTTCCAG 45TGGAAGCACCAGGAACCCT AGGGTTCCTGGTGCTTCCA 46 GGAAGCACCAGGAACCCTGCAGGGTTCCTGGTGCTTCC 47 GAAGCACCAGGAACCCTGG CCAGGGTTCCTGGTGCTTC 48AAGCACCAGGAACCCTGGG CCCAGGGTTCCTGGTGCTT 49 AGCACCAGGAACCCTGGGGCCCCAGGGTTCCTGGTGCT 50 GCACCAGGAACCCTGGGGA TCCCCAGGGTTCCTGGTGC 51CACCAGGAACCCTGGGGAT ATCCCCAGGGTTCCTGGTG 52 ACCAGGAACCCTGGGGATGCATCCCCAGGGTTCCTGGT 53 CCAGGAACCCTGGGGATGG CCATCCCCAGGGTTCCTGG 54CAGGAACCCTGGGGATGGG CCCATCCCCAGGGTTCCTG 55 AGGAACCCTGGGGATGGGGCCCCATCCCCAGGGTTCCT 56 GGAACCCTGGGGATGGGGC GCCCCATCCCCAGGGTTCC 57GAACCCTGGGGATGGGGCA TGCCCCATCCCCAGGGTTC 58 AACCCTGGGGATGGGGCAGCTGCCCCATCCCCAGGGTT 59 ACCCTGGGGATGGGGCAGA TCTGCCCCATCCCCAGGGT 60CCCTGGGGATGGGGCAGAC GTCTGCCCCATCCCCAGGG 61 CCTGGGGATGGGGCAGACCGGTCTGCCCCATCCCCAGG 62 CTGGGGATGGGGCAGACCC GGGTCTGCCCCATCCCCAG 63TGGGGATGGGGCAGACCCT AGGGTCTGCCCCATCCCCA 64 GGGGATGGGGCAGACCCTCGAGGGTCTGCCCCATCCCC 65 GGGATGGGGCAGACCCTCA TGAGGGTCTGCCCCATCCC 66GGATGGGGCAGACCCTCAC GTGAGGGTCTGCCCCATCC 67 GATGGGGCAGACCCTCACATGTGAGGGTCTGCCCCATC 68 ATGGGGCAGACCCTCACAG CTGTGAGGGTCTGCCCCAT 69TGGGGCAGACCCTCACAGC GCTGTGAGGGTCTGCCCCA 70 GGGGCAGACCCTCACAGCCGGCTGTGAGGGTCTGCCCC 71 GGGCAGACCCTCACAGCCC GGGCTGTGAGGGTCTGCCC 72GGCAGACCCTCACAGCCCG CGGGCTGTGAGGGTCTGCC 73 GCAGACCCTCACAGCCCGGCCGGGCTGTGAGGGTCTGC 74 CAGACCCTCACAGCCCGGG CCCGGGCTGTGAGGGTCTG 75AGACCCTCACAGCCCGGGG CCCCGGGCTGTGAGGGTCT 76 GACCCTCACAGCCCGGGGTACCCCGGGCTGTGAGGGTC 77 ACCCTCACAGCCCGGGGTC GACCCCGGGCTGTGAGGGT 78CCCTCACAGCCCGGGGTCT AGACCCCGGGCTGTGAGGG 79 CCTCACAGCCCGGGGTCTGCAGACCCCGGGCTGTGAGG 80 CTCACAGCCCGGGGTCTGG CCAGACCCCGGGCTGTGAG 81TCACAGCCCGGGGTCTGGA TCCAGACCCCGGGCTGTGA 82 CACAGCCCGGGGTCTGGAGCTCCAGACCCCGGGCTGTG 83 ACAGCCCGGGGTCTGGAGC GCTCCAGACCCCGGGCTGT 84CAGCCCGGGGTCTGGAGCC GGCTCCAGACCCCGGGCTG 85 AGCCCGGGGTCTGGAGCCGCGGCTCCAGACCCCGGGCT 86 GCCCGGGGTCTGGAGCCGG CCGGCTCCAGACCCCGGGC 87CCCGGGGTCTGGAGCCGGT ACCGGCTCCAGACCCCGGG 88 CCGGGGTCTGGAGCCGGTGCACCGGCTCCAGACCCCGG 89 CGGGGTCTGGAGCCGGTGT ACACCGGCTCCAGACCCCG 90GGGGTCTGGAGCCGGTGTC GACACCGGCTCCAGACCCC 91 GGGTCTGGAGCCGGTGTCGCGACACCGGCTCCAGACCC 92 GGTCTGGAGCCGGTGTCGG CCGACACCGGCTCCAGACC 93GTCTGGAGCCGGTGTCGGA TCCGACACCGGCTCCAGAC 94 TCTGGAGCCGGTGTCGGAGCTCCGACACCGGCTCCAGA 95 CTGGAGCCGGTGTCGGAGC GCTCCGACACCGGCTCCAG 96TGGAGCCGGTGTCGGAGCT AGCTCCGACACCGGCTCCA 97 GGAGCCGGTGTCGGAGCTCGAGCTCCGACACCGGCTCC 98 GAGCCGGTGTCGGAGCTCA TGAGCTCCGACACCGGCTC 99AGCCGGTGTCGGAGCTCAT ATGAGCTCCGACACCGGCT 100 GCCGGTGTCGGAGCTCATCGATGAGCTCCGACACCGGC 101 CCGGTGTCGGAGCTCATCT AGATGAGCTCCGACACCGG 102CGGTGTCGGAGCTCATCTG CAGATGAGCTCCGACACCG 103 GGTGTCGGAGCTCATCTGGCCAGATGAGCTCCGACACC 104 GTGTCGGAGCTCATCTGGG CCCAGATGAGCTCCGACAC 105TGTCGGAGCTCATCTGGGC GCCCAGATGAGCTCCGACA 106 GTCGGAGCTCATCTGGGCCGGCCCAGATGAGCTCCGAC 107 TCGGAGCTCATCTGGGCCC GGGCCCAGATGAGCTCCGA 108CGGAGCTCATCTGGGCCCA TGGGCCCAGATGAGCTCCG 109 GGAGCTCATCTGGGCCCATATGGGCCCAGATGAGCTCC 110 GAGCTCATCTGGGCCCATG CATGGGCCCAGATGAGCTC 111AGCTCATCTGGGCCCATGA TCATGGGCCCAGATGAGCT 112 GCTCATCTGGGCCCATGACGTCATGGGCCCAGATGAGC 113 CTCATCTGGGCCCATGACC GGTCATGGGCCCAGATGAG 114TCATCTGGGCCCATGACCT AGGTCATGGGCCCAGATGA 115 CATCTGGGCCCATGACCTCGAGGTCATGGGCCCAGATG 116 ATCTGGGCCCATGACCTCT AGAGGTCATGGGCCCAGAT 117TCTGGGCCCATGACCTCTC GAGAGGTCATGGGCCCAGA 118 CTGGGCCCATGACCTCTCCGGAGAGGTCATGGGCCCAG 119 TGGGCCCATGACCTCTCCA TGGAGAGGTCATGGGCCCA 120GGGCCCATGACCTCTCCAG CTGGAGAGGTCATGGGCCC 121 GGCCCATGACCTCTCCAGATCTGGAGAGGTCATGGGCC 122 GCCCATGACCTCTCCAGAC GTCTGGAGAGGTCATGGGC 123CCCATGACCTCTCCAGACA TGTCTGGAGAGGTCATGGG 124 CCATGACCTCTCCAGACATATGTCTGGAGAGGTCATGG 125 CATGACCTCTCCAGACATT AATGTCTGGAGAGGTCATG 126ATGACCTCTCCAGACATTT AAATGTCTGGAGAGGTCAT 127 TGACCTCTCCAGACATTTGCAAATGTCTGGAGAGGTCA 128 GACCTCTCCAGACATTTGG CCAAATGTCTGGAGAGGTC 129ACCTCTCCAGACATTTGGC GCCAAATGTCTGGAGAGGT 130 CCTCTCCAGACATTTGGCATGCCAAATGTCTGGAGAGG 131 CTCTCCAGACATTTGGCAA TTGCCAAATGTCTGGAGAG 132TCTCCAGACATTTGGCAAA TTTGCCAAATGTCTGGAGA 133 CTCCAGACATTTGGCAAAATTTTGCCAAATGTCTGGAG 134 TCCAGACATTTGGCAAAAT ATTTTGCCAAATGTCTGGA 135CCAGACATTTGGCAAAATC GATTTTGCCAAATGTCTGG 136 CAGACATTTGGCAAAATCATGATTTTGCCAAATGTCTG 137 AGACATTTGGCAAAATCAA TTGATTTTGCCAAATGTCT 138GACATTTGGCAAAATCAAG CTTGATTTTGCCAAATGTC 139 ACATTTGGCAAAATCAAGGCCTTGATTTTGCCAAATGT 140 CATTTGGCAAAATCAAGGC GCCTTGATTTTGCCAAATG 141ATTTGGCAAAATCAAGGCC GGCCTTGATTTTGCCAAAT 142 TTTGGCAAAATCAAGGCCCGGGCCTTGATTTTGCCAAA 143 TTGGCAAAATCAAGGCCCT AGGGCCTTGATTTTGCCAA 144TGGCAAAATCAAGGCCCTT AAGGGCCTTGATTTTGCCA 145 GGCAAAATCAAGGCCCTTATAAGGGCCTTGATTTTGCC 146 GCAAAATCAAGGCCCTTAG CTAAGGGCCTTGATTTTGC 147CAAAATCAAGGCCCTTAGA TCTAAGGGCCTTGATTTTG 148 AAAATCAAGGCCCTTAGACGTCTAAGGGCCTTGATTTT 149 AAATCAAGGCCCTTAGACC GGTCTAAGGGCCTTGATTT 150AATCAAGGCCCTTAGACCA TGGTCTAAGGGCCTTGATT 151 ATCAAGGCCCTTAGACCAGCTGGTCTAAGGGCCTTGAT 152 TCAAGGCCCTTAGACCAGG CCTGGTCTAAGGGCCTTGA 153CAAGGCCCTTAGACCAGGG CCCTGGTCTAAGGGCCTTG 154 AAGGCCCTTAGACCAGGGATCCCTGGTCTAAGGGCCTT 155 AGGCCCTTAGACCAGGGAC GTCCCTGGTCTAAGGGCCT 156GGCCCTTAGACCAGGGACA TGTCCCTGGTCTAAGGGCC 157 GCCCTTAGACCAGGGACAGCTGTCCCTGGTCTAAGGGC 158 CCCTTAGACCAGGGACAGA TCTGTCCCTGGTCTAAGGG 159CCTTAGACCAGGGACAGAC GTCTGTCCCTGGTCTAAGG 160 CTTAGACCAGGGACAGACCGGTCTGTCCCTGGTCTAAG 161 TTAGACCAGGGACAGACCC GGGTCTGTCCCTGGTCTAA 162TAGACCAGGGACAGACCCA TGGGTCTGTCCCTGGTCTA 163 AGACCAGGGACAGACCCAATTGGGTCTGTCCCTGGTCT 164 GACCAGGGACAGACCCAAG CTTGGGTCTGTCCCTGGTC 165ACCAGGGACAGACCCAAGC GCTTGGGTCTGTCCCTGGT 166 CCAGGGACAGACCCAAGCCGGCTTGGGTCTGTCCCTGG 167 CAGGGACAGACCCAAGCCC GGGCTTGGGTCTGTCCCTG 168AGGGACAGACCCAAGCCCA TGGGCTTGGGTCTGTCCCT 169 GGGACAGACCCAAGCCCAGCTGGGCTTGGGTCTGTCCC 170 GGACAGACCCAAGCCCAGG CCTGGGCTTGGGTCTGTCC 171GACAGACCCAAGCCCAGGC GCCTGGGCTTGGGTCTGTC 172 ACAGACCCAAGCCCAGGCCGGCCTGGGCTTGGGTCTGT 173 CAGACCCAAGCCCAGGCCC GGGCCTGGGCTTGGGTCTG 174AGACCCAAGCCCAGGCCCT AGGGCCTGGGCTTGGGTCT 175 GACCCAAGCCCAGGCCCTCGAGGGCCTGGGCTTGGGTC 176 ACCCAAGCCCAGGCCCTCC GGAGGGCCTGGGCTTGGGT 177CCCAAGCCCAGGCCCTCCC GGGAGGGCCTGGGCTTGGG 178 CCAAGCCCAGGCCCTCCCATGGGAGGGCCTGGGCTTGG 179 CAAGCCCAGGCCCTCCCAG CTGGGAGGGCCTGGGCTTG 180AAGCCCAGGCCCTCCCAGA TCTGGGAGGGCCTGGGCTT 181 AGCCCAGGCCCTCCCAGAGCTCTGGGAGGGCCTGGGCT 182 GCCCAGGCCCTCCCAGAGG CCTCTGGGAGGGCCTGGGC 183CCCAGGCCCTCCCAGAGGT ACCTCTGGGAGGGCCTGGG 184 CCAGGCCCTCCCAGAGGTCGACCTCTGGGAGGGCCTGG 185 CAGGCCCTCCCAGAGGTCC GGACCTCTGGGAGGGCCTG 186AGGCCCTCCCAGAGGTCCT AGGACCTCTGGGAGGGCCT 187 GGCCCTCCCAGAGGTCCTATAGGACCTCTGGGAGGGCC 188 GCCCTCCCAGAGGTCCTAG CTAGGACCTCTGGGAGGGC 189CCCTCCCAGAGGTCCTAGG CCTAGGACCTCTGGGAGGG 190 CCTCCCAGAGGTCCTAGGATCCTAGGACCTCTGGGAGG 191 CTCCCAGAGGTCCTAGGAC GTCCTAGGACCTCTGGGAG 192TCCCAGAGGTCCTAGGACG CGTCCTAGGACCTCTGGGA 193 CCCAGAGGTCCTAGGACGCGCGTCCTAGGACCTCTGGG 194 CCAGAGGTCCTAGGACGCA TGCGTCCTAGGACCTCTGG 195CAGAGGTCCTAGGACGCAA TTGCGTCCTAGGACCTCTG 196 AGAGGTCCTAGGACGCAACGTTGCGTCCTAGGACCTCT 197 GAGGTCCTAGGACGCAACC GGTTGCGTCCTAGGACCTC 198AGGTCCTAGGACGCAACCC GGGTTGCGTCCTAGGACCT 199 GGTCCTAGGACGCAACCCTAGGGTTGCGTCCTAGGACC 200 GTCCTAGGACGCAACCCTT AAGGGTTGCGTCCTAGGAC 201TCCTAGGACGCAACCCTTT AAAGGGTTGCGTCCTAGGA 202 CCTAGGACGCAACCCTTTGCAAAGGGTTGCGTCCTAGG 203 CTAGGACGCAACCCTTTGT ACAAAGGGTTGCGTCCTAG 204TAGGACGCAACCCTTTGTG CACAAAGGGTTGCGTCCTA 205 AGGACGCAACCCTTTGTGCGCACAAAGGGTTGCGTCCT 206 GGACGCAACCCTTTGTGCC GGCACAAAGGGTTGCGTCC 207GACGCAACCCTTTGTGCCC GGGCACAAAGGGTTGCGTC 208 ACGCAACCCTTTGTGCCCTAGGGCACAAAGGGTTGCGT 209 CGCAACCCTTTGTGCCCTT AAGGGCACAAAGGGTTGCG 210GCAACCCTTTGTGCCCTTG CAAGGGCACAAAGGGTTGC 211 CAACCCTTTGTGCCCTTGGCCAAGGGCACAAAGGGTTG 212 AACCCTTTGTGCCCTTGGG CCCAAGGGCACAAAGGGTT 213ACCCTTTGTGCCCTTGGGC GCCCAAGGGCACAAAGGGT 214 CCCTTTGTGCCCTTGGGCTAGCCCAAGGGCACAAAGGG 215 CCTTTGTGCCCTTGGGCTC GAGCCCAAGGGCACAAAGG 216CTTTGTGCCCTTGGGCTCT AGAGCCCAAGGGCACAAAG 217 TTTGTGCCCTTGGGCTCTGCAGAGCCCAAGGGCACAAA 218 TTGTGCCCTTGGGCTCTGG CCAGAGCCCAAGGGCACAA 219TGTGCCCTTGGGCTCTGGA TCCAGAGCCCAAGGGCACA 220 GTGCCCTTGGGCTCTGGAATTCCAGAGCCCAAGGGCAC 221 TGCCCTTGGGCTCTGGAAG CTTCCAGAGCCCAAGGGCA 222GCCCTTGGGCTCTGGAAGA TCTTCCAGAGCCCAAGGGC 223 CCCTTGGGCTCTGGAAGAGCTCTTCCAGAGCCCAAGGG 224 CCTTGGGCTCTGGAAGAGG CCTCTTCCAGAGCCCAAGG 225CTTGGGCTCTGGAAGAGGT ACCTCTTCCAGAGCCCAAG 226 TTGGGCTCTGGAAGAGGTTAACCTCTTCCAGAGCCCAA 227 TGGGCTCTGGAAGAGGTTT AAACCTCTTCCAGAGCCCA 228GGGCTCTGGAAGAGGTTTG CAAACCTCTTCCAGAGCCC 229 GGCTCTGGAAGAGGTTTGGCCAAACCTCTTCCAGAGCC 230 GCTCTGGAAGAGGTTTGGG CCCAAACCTCTTCCAGAGC 231CTCTGGAAGAGGTTTGGGA TCCCAAACCTCTTCCAGAG 232 TCTGGAAGAGGTTTGGGAATTCCCAAACCTCTTCCAGA 233 CTGGAAGAGGTTTGGGAAG CTTCCCAAACCTCTTCCAG 234TGGAAGAGGTTTGGGAAGG CCTTCCCAAACCTCTTCCA 235 GGAAGAGGTTTGGGAAGGGCCCTTCCCAAACCTCTTCC 236 GAAGAGGTTTGGGAAGGGT ACCCTTCCCAAACCTCTTC 237AAGAGGTTTGGGAAGGGTT AACCCTTCCCAAACCTCTT 238 AGAGGTTTGGGAAGGGTTTAAACCCTTCCCAAACCTCT 239 GAGGTTTGGGAAGGGTTTG CAAACCCTTCCCAAACCTC 240AGGTTTGGGAAGGGTTTGG CCAAACCCTTCCCAAACCT 241 GGTTTGGGAAGGGTTTGGGCCCAAACCCTTCCCAAACC 242 GTTTGGGAAGGGTTTGGGG CCCCAAACCCTTCCCAAAC 243TTTGGGAAGGGTTTGGGGT ACCCCAAACCCTTCCCAAA 244 TTGGGAAGGGTTTGGGGTGCACCCCAAACCCTTCCCAA 245 TGGGAAGGGTTTGGGGTGG CCACCCCAAACCCTTCCCA 246GGGAAGGGTTTGGGGTGGA TCCACCCCAAACCCTTCCC 247 GGAAGGGTTTGGGGTGGAATTCCACCCCAAACCCTTCC 248 GAAGGGTTTGGGGTGGAAG CTTCCACCCCAAACCCTTC 249AAGGGTTTGGGGTGGAAGA TCTTCCACCCCAAACCCTT 250 AGGGTTTGGGGTGGAAGATATCTTCCACCCCAAACCCT 251 GGGTTTGGGGTGGAAGATG CATCTTCCACCCCAAACCC 252GGTTTGGGGTGGAAGATGG CCATCTTCCACCCCAAACC 253 GTTTGGGGTGGAAGATGGCGCCATCTTCCACCCCAAAC 254 TTTGGGGTGGAAGATGGCA TGCCATCTTCCACCCCAAA 255TTGGGGTGGAAGATGGCAA TTGCCATCTTCCACCCCAA 256 TGGGGTGGAAGATGGCAAATTTGCCATCTTCCACCCCA 257 GGGGTGGAAGATGGCAAAG CTTTGCCATCTTCCACCCC 258GGGTGGAAGATGGCAAAGA TCTTTGCCATCTTCCACCC 259 GGTGGAAGATGGCAAAGAGCCTCTTTGCCATCTTCCACC 260 GTGGAAGATGGCAAAGAGC GCTCTTTGCCATCTTCCAC 261TGGAAGATGGCAAAGAGCA TGCTCTTTGCCATCTTCCA 262 GGAAGATGGCAAAGAGCAGCTGCTCTTTGCCATCTTCC 263 GAAGATGGCAAAGAGCAGC GCTGCTCTTTGCCATCTTC 264AAGATGGCAAAGAGCAGCT AGCTGCTCTTTGCCATCTT 265 AGATGGCAAAGAGCAGCTTAAGCTGCTCTTTGCCATCT 266 GATGGCAAAGAGCAGCTTG CAAGCTGCTCTTTGCCATC 267ATGGCAAAGAGCAGCTTGG CCAAGCTGCTCTTTGCCAT 268 TGGCAAAGAGCAGCTTGGCGCCAAGCTGCTCTTTGCCA 269 GGCAAAGAGCAGCTTGGCC GGCCAAGCTGCTCTTTGCC 270GCAAAGAGCAGCTTGGCCA TGGCCAAGCTGCTCTTTGC 271 CAAAGAGCAGCTTGGCCAGCTGGCCAAGCTGCTCTTTG 272 AAAGAGCAGCTTGGCCAGG CCTGGCCAAGCTGCTCTTT 273AAGAGCAGCTTGGCCAGGT ACCTGGCCAAGCTGCTCTT 274 AGAGCAGCTTGGCCAGGTGCACCTGGCCAAGCTGCTCT 275 GAGCAGCTTGGCCAGGTGA TCACCTGGCCAAGCTGCTC 276AGCAGCTTGGCCAGGTGAG CTCACCTGGCCAAGCTGCT 277 GCAGCTTGGCCAGGTGAGGCCTCACCTGGCCAAGCTGC 278 CAGCTTGGCCAGGTGAGGA TCCTCACCTGGCCAAGCTG 279AGCTTGGCCAGGTGAGGAT ATCCTCACCTGGCCAAGCT 280 GCTTGGCCAGGTGAGGATGCATCCTCACCTGGCCAAGC 281 CTTGGCCAGGTGAGGATGA TCATCCTCACCTGGCCAAG 282TTGGCCAGGTGAGGATGAG CTCATCCTCACCTGGCCAA 283 TGGCCAGGTGAGGATGAGGCCTCATCCTCACCTGGCCA 284 GGCCAGGTGAGGATGAGGC GCCTCATCCTCACCTGGCC 285GCCAGGTGAGGATGAGGCA TGCCTCATCCTCACCTGGC 286 CCAGGTGAGGATGAGGCAGCTGCCTCATCCTCACCTGG 287 CAGGTGAGGATGAGGCAGG CCTGCCTCATCCTCACCTG 288AGGTGAGGATGAGGCAGGG CCCTGCCTCATCCTCACCT 289 GGTGAGGATGAGGCAGGGCGCCCTGCCTCATCCTCACC 290 GTGAGGATGAGGCAGGGCA TGCCCTGCCTCATCCTCAC 291TGAGGATGAGGCAGGGCAG CTGCCCTGCCTCATCCTCA 292 GAGGATGAGGCAGGGCAGATCTGCCCTGCCTCATCCTC 293 AGGATGAGGCAGGGCAGAC GTCTGCCCTGCCTCATCCT 294GGATGAGGCAGGGCAGACA TGTCTGCCCTGCCTCATCC 295 GATGAGGCAGGGCAGACACGTGTCTGCCCTGCCTCATC 296 ATGAGGCAGGGCAGACACA TGTGTCTGCCCTGCCTCAT 297TGAGGCAGGGCAGACACAG CTGTGTCTGCCCTGCCTCA 298 GAGGCAGGGCAGACACAGGCCTGTGTCTGCCCTGCCTC 299 AGGCAGGGCAGACACAGGC GCCTGTGTCTGCCCTGCCT 300GGCAGGGCAGACACAGGCC GGCCTGTGTCTGCCCTGCC 301 GCAGGGCAGACACAGGCCATGGCCTGTGTCTGCCCTGC 302 CAGGGCAGACACAGGCCAG CTGGCCTGTGTCTGCCCTG 303AGGGCAGACACAGGCCAGT ACTGGCCTGTGTCTGCCCT 304 GGGCAGACACAGGCCAGTGCACTGGCCTGTGTCTGCCC 305 GGCAGACAGAGGCCAGTGG CCACTGGCCTGTGTCTGCC 306GCAGACACAGGCCAGTGGG CCCACTGGCCTGTGTCTGC 307 CAGACACAGGCCAGTGGGGCCCCACTGGCCTGTGTCTG 308 AGACACAGGCCAGTGGGGC GCCCCACTGGCCTGTGTCT 309GACACAGGCCAGTGGGGCG CGCCCCACTGGCCTGTGTC 310 ACACAGGCCAGTGGGGCGTACGCCCCACTGGCCTGTGT 311 CACAGGCCAGTGGGGCGTG CACGCCCCACTGGCCTGTG 312ACAGGCCAGTGGGGCGTGC GCACGCCCCACTGGCCTGT 313 CAGGCCAGTGGGGCGTGCCGGCACGCCCCACTGGCCTG 314 AGGCCAGTGGGGCGTGCCA TGGCACGCCCCACTGGCCT 315GGCCAGTGGGGCGTGCCAT ATGGCACGCCCCACTGGCC 316 GCCAGTGGGGCGTGCCATGCATGGCACGCCCCACTGGC 317 CCAGTGGGGCGTGCCATGT ACATGGCACGCCCCACTGG 318CAGTGGGGCGTGCCATGTG CACATGGCACGCCCCACTG 319 AGTGGGGCGTGCCATGTGCGCACATGGCACGCCCCACT 320 GTGGGGCGTGCCATGTGCC GGCACATGGCACGCCCCAC 321TGGGGCGTGCCATGTGCCA TGGCACATGGCACGCCCCA 322 GGGGCGTGCCATGTGCCACGTGGCACATGGCACGCCCC 323 GGGCGTGCCATGTGCCACA TGTGGCACATGGCACGCCC 324GGCGTGCCATGTGCCACAG CTGTGGCACATGGCACGCC 325 GCGTGCCATGTGCCACAGATCTGTGGCACATGGCACGC 326 CGTGCCATGTGCCACAGAT ATCTGTGGCACATGGCACG 327GTGCCATGTGCCACAGATG CATCTGTGGCACATGGCAC 328 TGCCATGTGCCACAGATGGCCATCTGTGGCACATGGCA 329 GCCATGTGCCACAGATGGA TCCATCTGTGGCACATGGC 330CCATGTGCCACAGATGGAG CTCCATCTGTGGCACATGG 331 CATGTGCCACAGATGGAGATCTCCATCTGTGGCACATG 332 ATGTGCCACAGATGGAGAG CTCTCCATCTGTGGCACAT 333TGTGCCACAGATGGAGAGG CCTCTCCATCTGTGGCACA 334 GTGCCACAGATGGAGAGGATCCTCTCCATCTGTGGCAC 335 TGCCACAGATGGAGAGGAC GTCCTCTCCATCTGTGGCA 336GCCACAGATGGAGAGGACC GGTCCTCTCCATCTGTGGC 337 CCACAGATGGAGAGGACCATGGTCCTCTCCATCTGTGG 338 CACAGATGGAGAGGACCAG CTGGTCCTCTCCATCTGTG 339ACAGATGGAGAGGACCAGG CCTGGTCCTCTCCATCTGT 340 CAGATGGAGAGGACCAGGATCCTGGTCCTCTCCATCTG 341 AGATGGAGAGGACCAGGAG CTCCTGGTCCTCTCCATCT 342GATGGAGAGGACCAGGAGC GCTCCTGGTCCTCTCCATC 343 ATGGAGAGGACCAGGAGCCGGCTCCTGGTCCTCTCCAT 344 TGGAGAGGACCAGGAGCCA TGGCTCCTGGTCCTCTCCA 345GGAGAGGACCAGGAGCCAG CTGGCTCCTGGTCCTCTCC 346 GAGAGGACCAGGAGCCAGTACTGGCTCCTGGTCCTCTC 347 AGAGGACCAGGAGCCAGTG CACTGGCTCCTGGTCCTCT 348GAGGACCAGGAGCCAGTGG CCACTGGCTCCTGGTCCTC 349 AGGACCAGGAGCCAGTGGCGCCACTGGCTCCTGGTCCT 350 GGACCAGGAGCCAGTGGCC GGCCACTGGCTCCTGGTCC 351GACCAGGAGCCAGTGGCCC GGGCCACTGGCTCCTGGTC 352 ACCAGGAGCCAGTGGCCCGCGGGCCACTGGCTCCTGGT 353 CCAGGAGCCAGTGGCCCGG CCGGGCCACTGGCTCCTGG 354CAGGAGCCAGTGGCCCGGC GCCGGGCCACTGGCTCCTG 355 AGGAGCCAGTGGCCCGGCATGCCGGGCCACTGGCTCCT 356 GGAGCCAGTGGCCCGGCAG CTGCCGGGCCACTGGCTCC 357GAGCCAGTGGCCCGGCAGG CCTGCCGGGCCACTGGCTC 358 AGCCAGTGGCCCGGCAGGCGCCTGCCGGGCCACTGGCT 359 GCCAGTGGCCCGGCAGGCA TGCCTGCCGGGCCACTGGC 360CCAGTGGCCCGGCAGGCAC GTGCCTGCCGGGCCACTGG 361 CAGTGGCCCGGCAGGCACATGTGCCTGCCGGGCCACTG 362 AGTGGCCCGGCAGGCACAG CTGTGCCTGCCGGGCCACT 363GTGGCCCGGCAGGCACAGC GCTGTGCCTGCCGGGCCAC 364 TGGCCCGGCAGGCACAGCCGGCTGTGCCTGCCGGGCCA 365 GGCCCGGCAGGCACAGCCC GGGCTGTGCCTGCCGGGCC 366GCCCGGCAGGCACAGCCCG CGGGCTGTGCCTGCCGGGC 367 CCCGGCAGGCACAGCCCGGCCGGGCTGTGCCTGCCGGG 368 CCGGCAGGCACAGCCCGGT ACCGGGCTGTGCCTGCCGG 369CGGCAGGCACAGCCCGGTT AACCGGGCTGTGCCTGCCG 370 GGCAGGCACAGCCCGGTTGCAACCGGGCTGTGCCTGCC 371 GCAGGCACAGCCCGGTTGG CCAACCGGGCTGTGCCTGC 372CAGGCACAGCCCGGTTGGC GCCAACCGGGCTGTGCCTG 373 AGGCACAGCCCGGTTGGCGCGCCAACCGGGCTGTGCCT 374 GGCACAGCCCGGTTGGCGT ACGCCAACCGGGCTGTGCC 375GCACAGCCCGGTTGGCGTG CACGCCAACCGGGCTGTGC 376 CACAGCCCGGTTGGCGTGGCCACGCCAACCGGGCTGTG 377 ACAGCCCGGTTGGCGTGGG CCCACGCCAACCGGGCTGT 378CAGCCCGGTTGGCGTGGGC GCCCACGCCAACCGGGCTG 379 AGCCCGGTTGGCGTGGGCCGGCCCACGCCAACCGGGCT 380 GCCCGGTTGGCGTGGGCCA TGGCCCACGCCAACCGGGC 381CCCGGTTGGCGTGGGCCAG CTGGCCCACGCCAACCGGG 382 CCGGTTGGCGTGGGCCAGATCTGGCCCACGCCAACCGG 383 CGGTTGGCGTGGGCCAGAG CTCTGGCCCACGCCAACCG 384GGTTGGCGTGGGCCAGAGC GCTCTGGCCCACGCCAACC 385 GTTGGCGTGGGCCAGAGCGCGCTCTGGCCCACGCCAAC 386 TTGGCGTGGGCCAGAGCGC GCGCTCTGGCCCACGCCAA 387TGGCGTGGGCCAGAGCGCC GGCGCTCTGGCCCACGCCA 388 GGCGTGGGCCAGAGCGCCCGGGCGCTCTGGCCCACGCC 389 GCGTGGGCCAGAGCGCCCA TGGGCGCTCTGGCCCACGC 390CGTGGGCCAGAGCGCCCAT ATGGGCGCTCTGGCCCACG 391 GTGGGCCAGAGCGCCCATCGATGGGCGCTCTGGCCCAC 392 TGGGCCAGAGCGCCCATCA TGATGGGCGCTCTGGCCCA 393GGGCCAGAGCGCCCATCAC GTGATGGGCGCTCTGGCCC 394 GGCCAGAGCGCCCATCACTAGTGATGGGCGCTCTGGCC 395 GCCAGAGCGCCCATCACTG CAGTGATGGGCGCTCTGGC 396CCAGAGCGCCCATCACTGA TCAGTGATGGGCGCTCTGG 397 CAGAGCGCCCATCACTGACGTCAGTGATGGGCGCTCTG 398 AGAGCGCCCATCACTGACC GGTCAGTGATGGGCGCTCT 399GAGCGCCCATCACTGACCC GGGTCAGTGATGGGCGCTC 400 AGCGCCCATCACTGACCCGCGGGTCAGTGATGGGCGCT 401 GCGCCCATCACTGACCCGT ACGGGTCAGTGATGGGCGC 402CGCCCATCACTGACCCGTG CACGGGTCAGTGATGGGCG 403 GCCCATCACTGACCCGTGATCACGGGTCAGTGATGGGC 404 CCCATCACTGACCCGTGAG CTCACGGGTCAGTGATGGG 405CCATCACTGACCCGTGAGA TCTCACGGGTCAGTGATGG 406 CATCACTGACCCGTGAGAATTCTCACGGGTCAGTGATG 407 ATCACTGACCCGTGAGAAC GTTCTCACGGGTCAGTGAT 408TCACTGACCCGTGAGAACT AGTTCTCACGGGTCAGTGA 409 CACTGACCCGTGAGAACTCGAGTTCTCACGGGTCAGTG 410 ACTGACCCGTGAGAACTCG CGAGTTCTCACGGGTCAGT 411CTGACCCGTGAGAACTCGA TCGAGTTCTCACGGGTCAG 412 TGACCCGTGAGAACTCGACGTCGAGTTCTCACGGGTCA 413 GACCCGTGAGAACTCGACT AGTCGAGTTCTCACGGGTC 414ACCCGTGAGAACTCGACTG CAGTCGAGTTCTCACGGGT 415 CCCGTGAGAACTCGACTGCGCAGTCGAGTTCTCACGGG 416 CCGTGAGAACTCGACTGCC GGCAGTCGAGTTCTCACGG 417CGTGAGAACTCGACTGCCC GGGCAGTCGAGTTCTCACG 418 GTGAGAACTCGACTGCCCCGGGGCAGTCGAGTTCTCAC 419 TGAGAACTCGACTGCCCCT AGGGGCAGTCGAGTTCTCA 420GAGAACTCGACTGCCCCTG CAGGGGCAGTCGAGTTCTC 421 AGAACTCGACTGCCCCTGCGCAGGGGCAGTCGAGTTCT 422 GAACTCGACTGCCCCTGCC GGCAGGGGCAGTCGAGTTC 423AACTCGACTGCCCCTGCCA TGGCAGGGGCAGTCGAGTT 424 ACTCGACTGCCCCTGCCAGCTGGCAGGGGCAGTCGAGT 425 CTCGACTGCCCCTGCCAGC GCTGGCAGGGGCAGTCGAG 426TCGACTGCCCCTGCCAGCT AGCTGGCAGGGGCAGTCGA 427 CGACTGCCCCTGCCAGCTCGAGCTGGCAGGGGCAGTCG 428 GACTGCCCCTGCCAGCTCT AGAGCTGGCAGGGGCAGTC 429ACTGCCCCTGCCAGCTCTG CAGAGCTGGCAGGGGCAGT 430 CTGCCCCTGCCAGCTCTGGCCAGAGCTGGCAGGGGCAG 431 TGCCCCTGCCAGCTCTGGC GCCAGAGCTGGCAGGGGCA 432GCCCCTGCCAGCTCTGGCA TGCCAGAGCTGGCAGGGGC 433 CCCCTGCCAGCTCTGGCACGTGCCAGAGCTGGCAGGGG 434 CCCTGCCAGCTCTGGCACT AGTGCCAGAGCTGGCAGGG 435CCTGCCAGCTCTGGCACTG CAGTGCCAGAGCTGGCAGG 436 CTGCCAGCTCTGGCACTGCGCAGTGCCAGAGCTGGCAG 437 TGCCAGCTCTGGCACTGCC GGCAGTGCCAGAGCTGGCA 438GCCAGCTCTGGCACTGCCC GGGCAGTGCCAGAGCTGGC 439 CCAGCTCTGGCACTGCCCCGGGGCAGTGCCAGAGCTGG 440 CAGCTCTGGCACTGCCCCC GGGGGCAGTGCCAGAGCTG 441AGCTCTGGCACTGCCCCCT AGGGGGCAGTGCCAGAGCT 442 GCTCTGGCACTGCCCCCTCGAGGGGGCAGTGCCAGAGC 443 CTCTGGCACTGCCCCCTCC GGAGGGGGCAGTGCCAGAG 444TCTGGCACTGCCCCCTCCC GGGAGGGGGCAGTGCCAGA 445 CTGGCACTGCCCCCTCCCATGGGAGGGGGCAGTGCCAG 446 TGGCACTGCCCCCTCCCAG CTGGGAGGGGGCAGTGCCA 447GGCACTGCCCCCTCCCAGC GCTGGGAGGGGGCAGTGCC 448 GCACTGCCCCCTCCCAGCCGGCTGGGAGGGGGCAGTGC 449 CACTGCCCCCTCCCAGCCG CGGCTGGGAGGGGGCAGTG 450ACTGCCCCCTCCCAGCCGC GCGGCTGGGAGGGGGCAGT 451 CTGCCCCCTCCCAGCCGCCGGCGGCTGGGAGGGGGCAG 452 TGCCCCCTCCCAGCCGCCC GGGCGGCTGGGAGGGGGCA 453GCCCCCTCCCAGCCGCCCC GGGGCGGCTGGGAGGGGGC 454 CCCCCTCCCAGCCGCCCCGCGGGGCGGCTGGGAGGGGG 455 CCCCTCCCAGCCGCCCCGC GCGGGGCGGCTGGGAGGGG 456CCCTCCCAGCCGCCCCGCC GGCGGGGCGGCTGGGAGGG 457 CCTCCCAGCCGCCCCGCCCGGGCGGGGCGGCTGGGAGG 458 CTCCCAGCCGCCCCGCCCT AGGGCGGGGCGGCTGGGAG 459TCCCAGCCGCCCCGCCCTA TAGGGCGGGGCGGCTGGGA 460 CCCAGCCGCCCCGCCCTAGCTAGGGCGGGGCGGCTGGG 461 CCAGCCGCCCCGCCCTAGC GCTAGGGCGGGGCGGCTGG 462CAGCCGCCCCGCCCTAGCA TGCTAGGGCGGGGCGGCTG 463 AGCCGCCCCGCCCTAGCACGTGCTAGGGCGGGGCGGCT 464 GCCGCCCCGCCCTAGCACC GGTGCTAGGGCGGGGCGGC 465CCGCCCCGCCCTAGCACCC GGGTGCTAGGGCGGGGCGG 466 CGCCCCGCCCTAGCACCCTAGGGTGCTAGGGCGGGGCG 467 GCCCCGCCCTAGCACCCTG CAGGGTGCTAGGGCGGGGC 468CCCCGCCCTAGCACCCTGG CCAGGGTGCTAGGGCGGGG 469 CCCGCCCTAGCACCCTGGGCCCAGGGTGCTAGGGCGGG 470 CCGCCCTAGCACCCTGGGG CCCCAGGGTGCTAGGGCGG 471CGCCCTAGCACCCTGGGGG CCCCCAGGGTGCTAGGGCG 472 GCCCTAGCACCCTGGGGGGCCCCCCAGGGTGCTAGGGC 473 CCCTAGCACCCTGGGGGGC GCCCCCCAGGGTGCTAGGG 474CCTAGCACCCTGGGGGGCA TGCCCCCCAGGGTGCTAGG 475 CTAGCACCCTGGGGGGCACGTGCCCCCCAGGGTGCTAG 476 TAGCACCCTGGGGGGCACC GGTGCCCCCCAGGGTGCTA 477AGCACCCTGGGGGGCACCC GGGTGCCCCCCAGGGTGCT 478 GCACCCTGGGGGGCACCCCGGGGTGCCCCCCAGGGTGC 479 CACCCTGGGGGGCACCCCG CGGGGTGCCCCCCAGGGTG 480ACCCTGGGGGGCACCCCGC GCGGGGTGCCCCCCAGGGT 481 CCCTGGGGGGCACCCCGCCGGCGGGGTGCCCCCCAGGG 482 CCTGGGGGGCACCCCGCCC GGGCGGGGTGCCCCCCAGG 483CTGGGGGGCACCCCGCCCA TGGGCGGGGTGCCCCCCAG 484 TGGGGGGCACCCCGCCCAATTGGGCGGGGTGCCCCCCA 485 GGGGGGCACCCCGCCCAAC GTTGGGCGGGGTGCCCCCC 486GGGGGCACCCCGCCCAACC GGTTGGGCGGGGTGCCCCC 487 GGGGCACCCCGCCCAACCGCGGTTGGGCGGGGTGCCCC 488 GGGCACCCCGCCCAACCGT ACGGTTGGGCGGGGTGCCC 489GGCACCCCGCCCAACCGTG CACGGTTGGGCGGGGTGCC 490 GCACCCCGCCCAACCGTGGCCACGGTTGGGCGGGGTGC 491 CACCCCGCCCAACCGTGGC GCCACGGTTGGGCGGGGTG 492ACCCCGCCCAACCGTGGCC GGCCACGGTTGGGCGGGGT 493 CCCCGCCCAACCGTGGCCTAGGCCACGGTTGGGCGGGG 494 CCCGCCCAACCGTGGCCTG CAGGCCACGGTTGGGCGGG 495CCGCCCAACCGTGGCCTGG CCAGGCCACGGTTGGGCGG 496 CGCCCAACCGTGGCCTGGTACCAGGCCACGGTTGGGCG 497 GCCCAACCGTGGCCTGGTC GACCAGGCCACGGTTGGGC 498CCCAACCGTGGCCTGGTCC GGACCAGGCCACGGTTGGG 499 CCAACCGTGGCCTGGTCCGCGGACCAGGCCACGGTTGG 500 CAACCGTGGCCTGGTCCGG CCGGACCAGGCCACGGTTG 501AACCGTGGCCTGGTCCGGC GCCGGACCAGGCCACGGTT 502 ACCGTGGCCTGGTCCGGCCGGCCGGACCAGGCCACGGT 503 CCGTGGCCTGGTCCGGCCC GGGCCGGACCAGGCCACGG 504CGTGGCCTGGTCCGGCCCC GGGGCCGGACCAGGCCACG 505 GTGGCCTGGTCCGGCCCCTAGGGGCCGGACCAGGCCAC 506 TGGCCTGGTCCGGCCCCTC GAGGGGCCGGACCAGGCCA 507GGCCTGGTCCGGCCCCTCC GGAGGGGCCGGACCAGGCC 508 GCCTGGTCCGGCCCCTCCCGGGAGGGGCCGGACCAGGC 509 CCTGGTCCGGCCCCTCCCG CGGGAGGGGCCGGACCAGG 510CTGGTCCGGCCCCTCCCGC GCGGGAGGGGCCGGACCAG 511 TGGTCCGGCCCCTCCCGCCGGCGGGAGGGGCCGGACCA 512 GGTCCGGCCCCTCCCGCCC GGGCGGGAGGGGCCGGACC 513GTCCGGCCCCTCCCGCCCT AGGGCGGGAGGGGCCGGAC 514 TCCGGCCCCTCCCGCCCTTAAGGGCGGGAGGGGCCGGA 515 CCGGCCCCTCCCGCCCTTT AAAGGGCGGGAGGGGCCGG 516CGGCCCCTCCCGCCCTTTG CAAAGGGCGGGAGGGGCCG 517 GGCCCCTCCCGCCCTTTGCGCAAAGGGCGGGAGGGGCC 518 GCCCCTCCCGCCCTTTGCT AGCAAAGGGCGGGAGGGGC 519CCCCTCCCGCCCTTTGCTC GAGCAAAGGGCGGGAGGGG 520 CCCTCCCGCCCTTTGCTCCGGAGCAAAGGGCGGGAGGG 521 CCTCCCGCCCTTTGCTCCA TGGAGCAAAGGGCGGGAGG 522CTCCCGCCCTTTGCTCCAG CTGGAGCAAAGGGCGGGAG 523 TCCCGCCCTTTGCTCCAGTACTGGAGCAAAGGGCGGGA 524 CCCGCCCTTTGCTCCAGTT AACTGGAGCAAAGGGCGGG 525CCGCCCTTTGCTCCAGTTC GAACTGGAGCAAAGGGCGG 526 CGCCCTTTGCTCCAGTTCCGGAACTGGAGCAAAGGGCG 527 GCCCTTTGCTCCAGTTCCC GGGAACTGGAGCAAAGGGC 528CCCTTTGCTCCAGTTCCCG CGGGAACTGGAGCAAAGGG 529 CCTTTGCTCCAGTTCCCGGCCGGGAACTGGAGCAAAGG 530 CTTTGCTCCAGTTCCCGGG CCCGGGAACTGGAGCAAAG 531TTTGCTCCAGTTCCCGGGC GCCCGGGAACTGGAGCAAA 532 TTGCTCCAGTTCCCGGGCTAGCCCGGGAACTGGAGCAA 533 TGCTCCAGTTCCCGGGCTT AAGCCCGGGAACTGGAGCA 534GCTCCAGTTCCCGGGCTTG CAAGCCCGGGAACTGGAGC 535 CTCCAGTTCCCGGGCTTGGCCAAGCCCGGGAACTGGAG 536 TCCAGTTCCCGGGCTTGGC GCCAAGCCCGGGAACTGGA 537CCAGTTCCCGGGCTTGGCA TGCCAAGCCCGGGAACTGG 538 CAGTTCCCGGGCTTGGCACGTGCCAAGCCCGGGAACTG 539 AGTTCCCGGGCTTGGCACC GGTGCCAAGCCCGGGAACT 540GTTCCCGGGCTTGGCACCT AGGTGCCAAGCCCGGGAAC 541 TTCCCGGGCTTGGCACCTATAGGTGCCAAGCCCGGGAA 542 TCCCGGGCTTGGCACCTAT ATAGGTGCCAAGCCCGGGA 543CCCGGGCTTGGCACCTATA TATAGGTGCCAAGCCCGGG 544 CCGGGCTTGGCACCTATAGCTATAGGTGCCAAGCCCGG 545 CGGGCTTGGCACCTATAGT ACTATAGGTGCCAAGCCCG 546GGGCTTGGCACCTATAGTG CACTATAGGTGCCAAGCCC 547 GGCTTGGCACCTATAGTGGCCACTATAGGTGCCAAGCC 548 GCTTGGCACCTATAGTGGG CCCACTATAGGTGCCAAGC 549CTTGGCACCTATAGTGGGG CCCCACTATAGGTGCCAAG 550 TTGGCACCTATAGTGGGGGCCCCCACTATAGGTGCCAA 551 TGGCACCTATAGTGGGGGT ACCCCCACTATAGGTGCCA 552GGCACCTATAGTGGGGGTG CACCCCCACTATAGGTGCC 553 GCACCTATAGTGGGGGTGCGCACCCCCACTATAGGTGC 554 CACCTATAGTGGGGGTGCC GGCACCCCCACTATAGGTG 555ACCTATAGTGGGGGTGCCG CGGCACCCCCACTATAGGT 556 CCTATAGTGGGGGTGCCGCGCGGCACCCCCACTATAGG 557 CTATAGTGGGGGTGCCGCC GGCGGCACCCCCACTATAG 558TATAGTGGGGGTGCCGCCC GGGCGGCACCCCCACTATA 559 ATAGTGGGGGTGCCGCCCGCGGGCGGCACCCCCACTAT 560 TAGTGGGGGTGCCGCCCGC GCGGGCGGCACCCCCACTA 561AGTGGGGGTGCCGCCCGCC GGCGGGCGGCACCCCCACT 562 GTGGGGGTGCCGCCCGCCTAGGCGGGCGGCACCCCCAC 563 TGGGGGTGCCGCCCGCCTG CAGGCGGGCGGCACCCCCA 564GGGGGTGCCGCCCGCCTGC GCAGGCGGGCGGCACCCCC 565 GGGGTGCCGCCCGCCTGCCGGCAGGCGGGCGGCACCCC 566 GGGTGCCGCCCGCCTGCCA TGGCAGGCGGGCGGCACCC 567GGTGCCGCCCGCCTGCCAG CTGGCAGGCGGGCGGCACC 568 GTGCCGCCCGCCTGCCAGGCCTGGCAGGCGGGCGGCAC 569 TGCCGCCCGCCTGCCAGGC GCCTGGCAGGCGGGCGGCA 570GCCGCCCGCCTGCCAGGCT AGCCTGGCAGGCGGGCGGC 571 CCGCCCGCCTGCCAGGCTCGAGCCTGGCAGGCGGGCGG 572 CGCCCGCCTGCCAGGCTCC GGAGCCTGGCAGGCGGGCG 573GCCCGCCTGCCAGGCTCCG CGGAGCCTGGCAGGCGGGC 574 CCCGCCTGCCAGGCTCCGGCCGGAGCCTGGCAGGCGGG 575 CCGCCTGCCAGGCTCCGGG CCCGGAGCCTGGCAGGCGG 576CGCCTGCCAGGCTCCGGGG CCCCGGAGCCTGGCAGGCG 577 GCCTGCCAGGCTCCGGGGCGCCCCGGAGCCTGGCAGGC 578 CCTGCCAGGCTCCGGGGCC GGCCCCGGAGCCTGGCAGG 579CTGCCAGGCTCCGGGGCCG CGGCCCCGGAGCCTGGCAG 580 TGCCAGGCTCCGGGGCCGGCCGGCCCCGGAGCCTGGCA 581 GCCAGGCTCCGGGGCCGGG CCCGGCCCCGGAGCCTGGC 582CCAGGCTCCGGGGCCGGGC GCCCGGCCCCGGAGCCTGG 583 CAGGCTCCGGGGCCGGGCCGGCCCGGCCCCGGAGCCTG 584 AGGCTCCGGGGCCGGGCCC GGGCCCGGCCCCGGAGCCT 585GGCTCCGGGGCCGGGCCCA TGGGCCCGGCCCCGGAGCC 586 GCTCCGGGGCCGGGCCCACGTGGGCCCGGCCCCGGAGC 587 CTCCGGGGCCGGGCCCACG CGTGGGCCCGGCCCCGGAG 588TCCGGGGCCGGGCCCACGG CCGTGGGCCCGGCCCCGGA 589 CCGGGGCCGGGCCCACGGGCCCGTGGGCCCGGCCCCGG 590 CGGGGCCGGGCCCACGGGA TCCCGTGGGCCCGGCCCCG 591GGGGCCGGGCCCACGGGAG CTCCCGTGGGCCCGGCCCC 592 GGGCCGGGCCCACGGGAGGCCTCCCGTGGGCCCGGCCC 593 GGCCGGGCCCACGGGAGGG CCCTCCCGTGGGCCCGGCC 594GCCGGGCCCACGGGAGGGT ACCCTCCCGTGGGCCCGGC 595 CCGGGCCCACGGGAGGGTGCACCCTCCCGTGGGCCCGG 596 CGGGCCCACGGGAGGGTGG CCACCCTCCCGTGGGCCCG 597GGGCCCACGGGAGGGTGGG CCCACCCTCCCGTGGGCCC 598 GGCCCACGGGAGGGTGGGGCCCCACCCTCCCGTGGGCC 599 GCCCACGGGAGGGTGGGGC GCCCCACCCTCCCGTGGGC 600CCCACGGGAGGGTGGGGCG CGCCCCACCCTCCCGTGGG 601 CCACGGGAGGGTGGGGCGGCCGCCCCACCCTCCCGTGG 602 CACGGGAGGGTGGGGCGGC GCCGCCCCACCCTCCCGTG 603ACGGGAGGGTGGGGCGGCT AGCCGCCCCACCCTCCCGT 604 CGGGAGGGTGGGGCGGCTGCAGCCGCCCCACCCTCCCG 605 GGGAGGGTGGGGCGGCTGG CCAGCCGCCCCACCCTCCC 606GGAGGGTGGGGCGGCTGGG CCCAGCCGCCCCACCCTCC 607 GAGGGTGGGGCGGCTGGGATCCCAGCCGCCCCACCCTC 608 AGGGTGGGGCGGCTGGGAA TTCCCAGCCGCCCCACCCT 609GGGTGGGGCGGCTGGGAAG CTTCCCAGCCGCCCCACCC 610 GGTGGGGCGGCTGGGAAGCGCTTCCCAGCCGCCCCACC 611 GTGGGGCGGCTGGGAAGCT AGCTTCCCAGCCGCCCCAC 612TGGGGCGGCTGGGAAGCTG CAGCTTCCCAGCCGCCCCA 613 GGGGCGGCTGGGAAGCTGGCCAGCTTCCCAGCCGCCCC 614 GGGCGGCTGGGAAGCTGGC GCCAGCTTCCCAGCCGCCC 615GGCGGCTGGGAAGCTGGCA TGCCAGCTTCCCAGCCGCC 616 GCGGCTGGGAAGCTGGCACGTGCCAGCTTCCCAGCCGC 617 CGGCTGGGAAGCTGGCACG CGTGCCAGCTTCCCAGCCG 618GGCTGGGAAGCTGGCACGC GCGTGCCAGCTTCCCAGCC 619 GCTGGGAAGCTGGCACGCTAGCGTGCCAGCTTCCCAGC 620 CTGGGAAGCTGGCACGCTG CAGCGTGCCAGCTTCCCAG 621TGGGAAGCTGGCACGCTGC GCAGCGTGCCAGCTTCCCA 622 GGGAAGCTGGCACGCTGCCGGCAGCGTGCCAGCTTCCC 623 GGAAGCTGGCACGCTGCCC GGGCAGCGTGCCAGCTTCC 624GAAGCTGGCACGCTGCCCC GGGGCAGCGTGCCAGCTTC 625 AAGCTGGCACGCTGCCCCGCGGGGCAGCGTGCCAGCTT 626 AGCTGGCACGCTGCCCCGG CCGGGGCAGCGTGCCAGCT 627GCTGGCACGCTGCCCCGGG CCCGGGGCAGCGTGCCAGC 628 CTGGCACGCTGCCCCGGGGCCCCGGGGCAGCGTGCCAG 629 TGGCACGCTGCCCCGGGGG CCCCCGGGGCAGCGTGCCA 630GGCACGCTGCCCCGGGGGA TCCCCCGGGGCAGCGTGCC 631 GCACGCTGCCCCGGGGGAGCTCCCCCGGGGCAGCGTGC 632 CACGCTGCCCCGGGGGAGC GCTCCCCCGGGGCAGCGTG 633ACGCTGCCCCGGGGGAGCC GGCTCCCCCGGGGCAGCGT 634 CGCTGCCCCGGGGGAGCCTAGGCTCCCCCGGGGCAGCG 635 GCTGCCCCGGGGGAGCCTC GAGGCTCCCCCGGGGCAGC 636CTGCCCCGGGGGAGCCTCT AGAGGCTCCCCCGGGGCAG 637 TGCCCCGGGGGAGCCTCTCGAGAGGCTCCCCCGGGGCA 638 GCCCCGGGGGAGCCTCTCT AGAGAGGCTCCCCCGGGGC 639CCCCGGGGGAGCCTCTCTC GAGAGAGGCTCCCCCGGGG 640 CCCGGGGGAGCCTCTCTCGCGAGAGAGGCTCCCCCGGG 641 CCGGGGGAGCCTCTCTCGG CCGAGAGAGGCTCCCCCGG 642CGGGGGAGCCTCTCTCGGC GCCGAGAGAGGCTCCCCCG 643 GGGGGAGCCTCTCTCGGCATGCCGAGAGAGGCTCCCCC 644 GGGGAGCCTCTCTCGGCAG CTGCCGAGAGAGGCTCCCC 645GGGAGCCTCTCTCGGCAGG CCTGCCGAGAGAGGCTCCC 646 GGAGCCTCTCTCGGCAGGCGCCTGCCGAGAGAGGCTCC 647 GAGCCTCTCTCGGCAGGCG CGCCTGCCGAGAGAGGCTC 648AGCCTCTCTCGGCAGGCGC GCGCCTGCCGAGAGAGGCT 649 GCCTCTCTCGGCAGGCGCCGGCGCCTGCCGAGAGAGGC 650 CCTCTCTCGGCAGGCGCCC GGGCGCCTGCCGAGAGAGG 651CTCTCTCGGCAGGCGCCCG CGGGCGCCTGCCGAGAGAG 652 TCTCTCGGCAGGCGCCCGGCCGGGCGCCTGCCGAGAGA 653 CTCTCGGCAGGCGCCCGGG CCCGGGCGCCTGCCGAGAG 654TCTCGGCAGGCGCCCGGGT ACCCGGGCGCCTGCCGAGA 655 CTCGGCAGGCGCCCGGGTGCACCCGGGCGCCTGCCGAG 656 TCGGCAGGCGCCCGGGTGC GCACCCGGGCGCCTGCCGA 657CGGCAGGCGCCCGGGTGCC GGCACCCGGGCGCCTGCCG 658 GGCAGGCGCCCGGGTGCCGCGGCACCCGGGCGCCTGCC 659 GCAGGCGCCCGGGTGCCGC GCGGCACCCGGGCGCCTGC 660CAGGCGCCCGGGTGCCGCG CGCGGCACCCGGGCGCCTG 661 AGGCGCCCGGGTGCCGCGGCCGCGGCACCCGGGCGCCT 662 GGCGCCCGGGTGCCGCGGG CCCGCGGCACCCGGGCGCC 663GCGCCCGGGTGCCGCGGGG CCCCGCGGCACCCGGGCGC 664 CGCCCGGGTGCCGCGGGGGCCCCCGCGGCACCCGGGCG 665 GCCCGGGTGCCGCGGGGGG CCCCCCGCGGCACCCGGGC 666CCCGGGTGCCGCGGGGGGG CCCCCCCGCGGCACCCGGG 667 CCGGGTGCCGCGGGGGGGATCCCCCCCGCGGCACCCGG 668 CGGGTGCCGCGGGGGGGAG CTCCCCCCCGCGGCACCCG 669GGGTGCCGCGGGGGGGAGG CCTCCCCCCCGCGGCACCC 670 GGTGCCGCGGGGGGGAGGGCCCTCCCCCCCGCGGCACC 671 GTGCCGCGGGGGGGAGGGG CCCCTCCCCCCCGCGGCAC 672TGCCGCGGGGGGGAGGGGG CCCCCTCCCCCCCGCGGCA 673 GCCGCGGGGGGGAGGGGGATCCCCCTCCCCCCCGCGGC 674 CCGCGGGGGGGAGGGGGAA TTCCCCCTCCCCCCCGCGG 675CGCGGGGGGGAGGGGGAAC GTTCCCCCTCCCCCCCGCG 676 GCGGGGGGGAGGGGGAACATGTTCCCCCTCCCCCCCGC 677 CGGGGGGGAGGGGGAACAA TTGTTCCCCCTCCCCCCCG 678GGGGGGGAGGGGGAACAAA TTTGTTCCCCCTCCCCCCC 679 GGGGGGAGGGGGAACAAAGCTTTGTTCCCCCTCCCCCC 680 GGGGGAGGGGGAACAAAGG CCTTTGTTCCCCCTCCCCC 681GGGGAGGGGGAACAAAGGG CCCTTTGTTCCCCCTCCCC 682 GGGAGGGGGAACAAAGGGCGCCCTTTGTTCCCCCTCCC 683 GGAGGGGGAACAAAGGGCT AGCCCTTTGTTCCCCCTCC 684GAGGGGGAACAAAGGGCTC GAGCCCTTTGTTCCCCCTC 685 AGGGGGAACAAAGGGCTCATGAGCCCTTTGTTCCCCCT 686 GGGGGAACAAAGGGCTCAT ATGAGCCCTTTGTTCCCCC 687GGGGAACAAAGGGCTCATT AATGAGCCCTTTGTTCCCC 688 GGGAACAAAGGGCTCATTCGAATGAGCCCTTTGTTCCC 689 GGAACAAAGGGCTCATTCT AGAATGAGCCCTTTGTTCC 690GAACAAAGGGCTCATTCTC GAGAATGAGCCCTTTGTTC 691 AACAAAGGGCTCATTCTCCGGAGAATGAGCCCTTTGTT 692 ACAAAGGGCTCATTCTCCC GGGAGAATGAGCCCTTTGT 693CAAAGGGCTCATTCTCCCC GGGGAGAATGAGCCCTTTG 694 AAAGGGCTCATTCTCCCCGCGGGGAGAATGAGCCCTTT 695 AAGGGCTCATTCTCCCCGT ACGGGGAGAATGAGCCCTT 696AGGGCTCATTCTCCCCGTG CACGGGGAGAATGAGCCCT 697 GGGCTCATTCTCCCCGTGCGCACGGGGAGAATGAGCCC 698 GGCTCATTCTCCCCGTGCG CGCACGGGGAGAATGAGCC 699GCTCATTCTCCCCGTGCGC GCGCACGGGGAGAATGAGC 700 CTCATTCTCCCCGTGCGCATGCGCACGGGGAGAATGAG 701 TCATTCTCCCCGTGCGCAG CTGCGCACGGGGAGAATGA 702CATTCTCCCCGTGCGCAGC GCTGCGCACGGGGAGAATG 703 ATTCTCCCCGTGCGCAGCCGGCTGCGCACGGGGAGAAT 704 TTCTCCCCGTGCGCAGCCG CGGCTGCGCACGGGGAGAA 705TCTCCCCGTGCGCAGCCGG CCGGCTGCGCACGGGGAGA 706 CTCCCCGTGCGCAGCCGGTACCGGCTGCGCACGGGGAG 707 TCCCCGTGCGCAGCCGGTG CACCGGCTGCGCACGGGGA 708CCCCGTGCGCAGCCGGTGG CCACCGGCTGCGCACGGGG 709 CCCGTGCGCAGCCGGTGGCGCCACCGGCTGCGCACGGG 710 CCGTGCGCAGCCGGTGGCA TGCCACCGGCTGCGCACGG 711CGTGCGCAGCCGGTGGCAT ATGCCACCGGCTGCGCACG 712 GTGCGCAGCCGGTGGCATCGATGCCACCGGCTGCGCAC 713 TGCGCAGCCGGTGGCATCG CGATGCCACCGGCTGCGCA 714GCGCAGCCGGTGGCATCGC GCGATGCCACCGGCTGCGC 715 CGCAGCCGGTGGCATCGCCGGCGATGCCACCGGCTGCG 716 GCAGCCGGTGGCATCGCCG CGGCGATGCCACCGGCTGC 717CAGCCGGTGGCATCGCCGG CCGGCGATGCCACCGGCTG 718 AGCCGGTGGCATCGCCGGGCCCGGCGATGCCACCGGCT 719 GCCGGTGGCATCGCCGGGG CCCCGGCGATGCCACCGGC 720CCGGTGGCATCGCCGGGGC GCCCCGGCGATGCCACCGG 721 CGGTGGCATCGCCGGGGCGCGCCCCGGCGATGCCACCG 722 GGTGGCATCGCCGGGGCGT ACGCCCCGGCGATGCCACC 723GTGGCATCGCCGGGGCGTT AACGCCCCGGCGATGCCAC 724 TGGCATCGCCGGGGCGTTGCAACGCCCCGGCGATGCCA 725 GGCATCGCCGGGGCGTTGG CCAACGCCCCGGCGATGCC 726GCATCGCCGGGGCGTTGGC GCCAACGCCCCGGCGATGC 727 CATCGCCGGGGCGTTGGCGCGCCAACGCCCCGGCGATG 728 ATCGCCGGGGCGTTGGCGG CCGCCAACGCCCCGGCGAT 729TCGCCGGGGCGTTGGCGGA TCCGCCAACGCCCCGGCGA 730 CGCCGGGGCGTTGGCGGAATTCCGCCAACGCCCCGGCG 731 GCCGGGGCGTTGGCGGAAG CTTCCGCCAACGCCCCGGC 732CCGGGGCGTTGGCGGAAGC GCTTCCGCCAACGCCCCGG 733 CGGGGCGTTGGCGGAAGCCGGCTTCCGCCAACGCCCCG 734 GGGGCGTTGGCGGAAGCCC GGGCTTCCGCCAACGCCCC 735GGGCGTTGGCGGAAGCCCC GGGGCTTCCGCCAACGCCC 736 GGCGTTGGCGGAAGCCCCCGGGGGCTTCCGCCAACGCC 737 GCGTTGGCGGAAGCCCCCG CGGGGGCTTCCGCCAACGC 738CGTTGGCGGAAGCCCCCGG CCGGGGGCTTCCGCCAACG 739 GTTGGCGGAAGCCCCCGGGCCCGGGGGCTTCCGCCAAC 740 TTGGCGGAAGCCCCCGGGG CCCCGGGGGCTTCCGCCAA 741TGGCGGAAGCCCCCGGGGC GCCCCGGGGGCTTCCGCCA 742 GGCGGAAGCCCCCGGGGCCGGCCCCGGGGGCTTCCGCC 743 GCGGAAGCCCCCGGGGCCC GGGCCCCGGGGGCTTCCGC 744CGGAAGCCCCCGGGGCCCG CGGGCCCCGGGGGCTTCCG 745 GGAAGCCCCCGGGGCCCGGCCGGGCCCCGGGGGCTTCC 746 GAAGCCCCCGGGGCCCGGG CCCGGGCCCCGGGGGCTTC 747AAGCCCCCGGGGCCCGGGA TCCCGGGCCCCGGGGGCTT 748 AGCCCCCGGGGCCCGGGAGCTCCCGGGCCCCGGGGGCT 749 GCCCCCGGGGCCCGGGAGG CCTCCCGGGCCCCGGGGGC 750CCCCCGGGGCCCGGGAGGG CCCTCCCGGGCCCCGGGGG 751 CCCCGGGGCCCGGGAGGGGCCCCTCCCGGGCCCCGGGG 752 CCCGGGGCCCGGGAGGGGG CCCCCTCCCGGGCCCCGGG 753CCGGGGCCCGGGAGGGGGC GCCCCCTCCCGGGCCCCGG 754 CGGGGCCCGGGAGGGGGCATGCCCCCTCCCGGGCCCCG 755 GGGGCCCGGGAGGGGGCAG CTGCCCCCTCCCGGGCCCC 756GGGCCCGGGAGGGGGCAGG CCTGCCCCCTCCCGGGCCC 757 GGCCCGGGAGGGGGCAGGCGCCTGCCCCCTCCCGGGCC 758 GCCCGGGAGGGGGCAGGCC GGCCTGCCCCCTCCCGGGC 759CCCGGGAGGGGGCAGGCCC GGGCCTGCCCCCTCCCGGG 760 CCGGGAGGGGGCAGGCCCATGGGCCTGCCCCCTCCCGG 761 CGGGAGGGGGCAGGCCCAG CTGGGCCTGCCCCCTCCCG 762GGGAGGGGGCAGGCCCAGG CCTGGGCCTGCCCCCTCCC 763 GGAGGGGGCAGGCCCAGGCGCCTGGGCCTGCCCCCTCC 764 GAGGGGGCAGGCCCAGGCG CGCCTGGGCCTGCCCCCTC 765AGGGGGCAGGCCCAGGCGC GCGCCTGGGCCTGCCCCCT 766 GGGGGCAGGCCCAGGCGCGCGCGCCTGGGCCTGCCCCC 767 GGGGCAGGCCCAGGCGCGG CCGCGCCTGGGCCTGCCCC 768GGGCAGGCCCAGGCGCGGC GCCGCGCCTGGGCCTGCCC 769 GGCAGGCCCAGGCGCGGCCGGCCGCGCCTGGGCCTGCC 770 GCAGGCCCAGGCGCGGCCG CGGCCGCGCCTGGGCCTGC 771CAGGCCCAGGCGCGGCCGC GCGGCCGCGCCTGGGCCTG 772 AGGCCCAGGCGCGGCCGCCGGCGGCCGCGCCTGGGCCT 773 GGCCCAGGCGCGGCCGCCG CGGCGGCCGCGCCTGGGCC 774GCCCAGGCGCGGCCGCCGA TCGGCGGCCGCGCCTGGGC 775 CCCAGGCGCGGCCGCCGAATTCGGCGGCCGCGCCTGGG 776 CCAGGCGCGGCCGCCGAAT ATTCGGCGGCCGCGCCTGG 777CAGGCGCGGCCGCCGAATC GATTCGGCGGCCGCGCCTG 778 AGGCGCGGCCGCCGAATCATGATTCGGCGGCCGCGCCT 779 GGCGCGGCCGCCGAATCAC GTGATTCGGCGGCCGCGCC 780GCGCGGCCGCCGAATCACG CGTGATTCGGCGGCCGCGC 781 CGCGGCCGCCGAATCACGGCCGTGATTCGGCGGCCGCG 782 GCGGCCGCCGAATCACGGG CCCGTGATTCGGCGGCCGC 783CGGCCGCCGAATCACGGGC GCCCGTGATTCGGCGGCCG 784 GGCCGCCGAATCACGGGCTAGCCCGTGATTCGGCGGCC 785 GCCGCCGAATCACGGGCTC GAGCCCGTGATTCGGCGGC 786CCGCCGAATCACGGGCTCC GGAGCCCGTGATTCGGCGG 787 CGCCGAATCACGGGCTCCTAGGAGCCCGTGATTCGGCG 788 GCCGAATCACGGGCTCCTG CAGGAGCCCGTGATTCGGC 789CCGAATCACGGGCTCCTGT ACAGGAGCCCGTGATTCGG 790 CGAATCACGGGCTCCTGTTAACAGGAGCCCGTGATTCG 791 GAATCACGGGCTCCTGTTT AAACAGGAGCCCGTGATTC 792AATCACGGGCTCCTGTTTC GAAACAGGAGCCCGTGATT 793 ATCACGGGCTCCTGTTTCCGGAAACAGGAGCCCGTGAT 794 TCACGGGCTCCTGTTTCCC GGGAAACAGGAGCCCGTGA 795CACGGGCTCCTGTTTCCCG CGGGAAACAGGAGCCCGTG 796 ACGGGCTCCTGTTTCCCGCGCGGGAAACAGGAGCCCGT 797 CGGGCTCCTGTTTCCCGCA TGCGGGAAACAGGAGCCCG 798GGGCTCCTGTTTCCCGCAG CTGCGGGAAACAGGAGCCC 799 GGCTCCTGTTTCCCGCAGGCCTGCGGGAAACAGGAGCC 800 GCTCCTGTTTCCCGCAGGG CCCTGCGGGAAACAGGAGC 801CTCCTGTTTCCCGCAGGGT ACCCTGCGGGAAACAGGAG 802 TCCTGTTTCCCGCAGGGTGCACCCTGCGGGAAACAGGA 803 CCTGTTTCCCGCAGGGTGC GCACCCTGCGGGAAACAGG 804CTGTTTCCCGCAGGGTGCT AGCACCCTGCGGGAAACAG 805 TGTTTCCCGCAGGGTGCTGCAGCACCCTGCGGGAAACA 806 GTTTCCCGCAGGGTGCTGG CCAGCACCCTGCGGGAAAC 807TTTCCCGCAGGGTGCTGGA TCCAGCACCCTGCGGGAAA 808 TTCCCGCAGGGTGCTGGAGCTCCAGCACCCTGCGGGAA 809 TCCCGCAGGGTGCTGGAGG CCTCCAGCACCCTGCGGGA 810CCCGCAGGGTGCTGGAGGA TCCTCCAGCACCCTGCGGG 811 CCGCAGGGTGCTGGAGGAGCTCCTCCAGCACCCTGCGG 812 CGCAGGGTGCTGGAGGAGG CCTCCTCCAGCACCCTGCG 813GCAGGGTGCTGGAGGAGGA TCCTCCTCCAGCACCCTGC 814 CAGGGTGCTGGAGGAGGAATTCCTCCTCCAGCACCCTG 815 AGGGTGCTGGAGGAGGAAA TTTCCTCCTCCAGCACCCT 816GGGTGCTGGAGGAGGAAAC GTTTCCTCCTCCAGCACCC 817 GGTGCTGGAGGAGGAAACCGGTTTCCTCCTCCAGCACC 818 GTGCTGGAGGAGGAAACCG CGGTTTCCTCCTCCAGCAC 819TGCTGGAGGAGGAAACCGG CCGGTTTCCTCCTCCAGCA 820 GCTGGAGGAGGAAACCGGCGCCGGTTTCCTCCTCCAGC 821 CTGGAGGAGGAAACCGGCG CGCCGGTTTCCTCCTCCAG 822TGGAGGAGGAAACCGGCGG CCGCCGGTTTCCTCCTCCA 823 GGAGGAGGAAACCGGCGGATCCGCCGGTTTCCTCCTCC 824 GAGGAGGAAACCGGCGGAG CTCCGCCGGTTTCCTCCTC 825AGGAGGAAACCGGCGGAGC GCTCCGCCGGTTTCCTCCT 826 GGAGGAAACCGGCGGAGCATGCTCCGCCGGTTTCCTCC 827 GAGGAAACCGGCGGAGCAG CTGCTCCGCCGGTTTCCTC 828AGGAAACCGGCGGAGCAGC GCTGCTCCGCCGGTTTCCT 829 GGAAACCGGCGGAGCAGCTAGCTGCTCCGCCGGTTTCC 830 GAAACCGGCGGAGCAGCTT AAGCTGCTCCGCCGGTTTC 831AAACCGGCGGAGCAGCTTC GAAGCTGCTCCGCCGGTTT 832 AACCGGCGGAGCAGCTTCCGGAAGCTGCTCCGCCGGTT 833 ACCGGCGGAGCAGCTTCCC GGGAAGCTGCTCCGCCGGT 834CCGGCGGAGCAGCTTCCCC GGGGAAGCTGCTCCGCCGG 835 CGGCGGAGCAGCTTCCCCATGGGGAAGCTGCTCCGCCG 836 GGCGGAGCAGCTTCCCCAC GTGGGGAAGCTGCTCCGCC 837GCGGAGCAGCTTCCCCACT AGTGGGGAAGCTGCTCCGC 838 CGGAGCAGCTTCCCCACTCGAGTGGGGAAGCTGCTCCG 839 GGAGCAGCTTCCCCACTCT AGAGTGGGGAAGCTGCTCC 840GAGCAGCTTCCCCACTCTC GAGAGTGGGGAAGCTGCTC 841 AGCAGCTTCCCCACTCTCATGAGAGTGGGGAAGCTGCT 842 GCAGCTTCCCCACTCTCAG CTGAGAGTGGGGAAGCTGC 843CAGCTTCCCCACTCTCAGT ACTGAGAGTGGGGAAGCTG 844 AGCTTCCCCACTCTCAGTTAACTGAGAGTGGGGAAGCT 845 GCTTCCCCACTCTCAGTTG CAACTGAGAGTGGGGAAGC 846CTTCCCCACTCTCAGTTGC GCAACTGAGAGTGGGGAAG 847 TTCCCCACTCTCAGTTGCGCGCAACTGAGAGTGGGGAA 848 TCCCCACTCTCAGTTGCGC GCGCAACTGAGAGTGGGGA 849CCCCACTCTCAGTTGCGCT AGCGCAACTGAGAGTGGGG 850 CCCACTCTCAGTTGCGCTTAAGCGCAACTGAGAGTGGG 851 CCACTCTCAGTTGCGCTTC GAAGCGCAACTGAGAGTGG 852CACTCTCAGTTGCGCTTCT AGAAGCGCAACTGAGAGTG 853 ACTCTCAGTTGCGCTTCTGCAGAAGCGCAACTGAGAGT 854 CTCTCAGTTGCGCTTCTGG CCAGAAGCGCAACTGAGAG 855TCTCAGTTGCGCTTCTGGC GCCAGAAGCGCAACTGAGA 856 CTCAGTTGCGCTTCTGGCGCGCCAGAAGCGCAACTGAG 857 TCAGTTGCGCTTCTGGCGA TCGCCAGAAGCGCAACTGA 858CAGTTGCGCTTCTGGCGAT ATCGCCAGAAGCGCAACTG 859 AGTTGCGCTTCTGGCGATGCATCGCCAGAAGCGCAACT 860 GTTGCGCTTCTGGCGATGG CCATCGCCAGAAGCGCAAC 861TTGCGCTTCTGGCGATGGC GCCATCGCCAGAAGCGCAA 862 TGCGCTTCTGGCGATGGCGCGCCATCGCCAGAAGCGCA 863 GCGCTTCTGGCGATGGCGA TCGCCATCGCCAGAAGCGC 864CGCTTCTGGCGATGGCGAT ATCGCCATCGCCAGAAGCG 865 GCTTCTGGCGATGGCGATCGATCGCCATCGCCAGAAGC 866 CTTCTGGCGATGGCGATCA TGATCGCCATCGCCAGAAG 867TTCTGGCGATGGCGATCAG CTGATCGCCATCGCCAGAA 868 TCTGGCGATGGCGATCAGATCTGATCGCCATCGCCAGA 869 CTGGCGATGGCGATCAGAG CTCTGATCGCCATCGCCAG 870TGGCGATGGCGATCAGAGG CCTCTGATCGCCATCGCCA 871 GGCGATGGCGATCAGAGGTACCTCTGATCGCCATCGCC 872 GCGATGGCGATCAGAGGTC GACCTCTGATCGCCATCGC 873CGATGGCGATCAGAGGTCC GGACCTCTGATCGCCATCG 874 GATGGCGATCAGAGGTCCTAGGACCTCTGATCGCCATC 875 ATGGCGATCAGAGGTCCTG CAGGACCTCTGATCGCCAT 876TGGCGATCAGAGGTCCTGC GCAGGACCTCTGATCGCCA 877 GGCGATCAGAGGTCCTGCTAGCAGGACCTCTGATCGCC 878 GCGATCAGAGGTCCTGCTG CAGCAGGACCTCTGATCGC 879CGATCAGAGGTCCTGCTGC GCAGCAGGACCTCTGATCG 880 GATCAGAGGTCCTGCTGCGCGCAGCAGGACCTCTGATC 881 ATCAGAGGTCCTGCTGCGC GCGCAGCAGGACCTCTGAT 882TCAGAGGTCCTGCTGCGCT AGCGCAGCAGGACCTCTGA 883 CAGAGGTCCTGCTGCGCTCGAGCGCAGCAGGACCTCTG 884 AGAGGTCCTGCTGCGCTCT AGAGCGCAGCAGGACCTCT 885GAGGTCCTGCTGCGCTCTC GAGAGCGCAGCAGGACCTC 886 AGGTCCTGCTGCGCTCTCCGGAGAGCGCAGCAGGACCT 887 GGTCCTGCTGCGCTCTCCG CGGAGAGCGCAGCAGGACC 888GTCCTGCTGCGCTCTCCGC GCGGAGAGCGCAGCAGGAC 889 TCCTGCTGCGCTCTCCGCCGGCGGAGAGCGCAGCAGGA 890 CCTGCTGCGCTCTCCGCCG CGGCGGAGAGCGCAGCAGG 891CTGCTGCGCTCTCCGCCGC GCGGCGGAGAGCGCAGCAG 892 TGCTGCGCTCTCCGCCGCGCGCGGCGGAGAGCGCAGCA 893 GCTGCGCTCTCCGCCGCGC GCGCGGCGGAGAGCGCAGC 894CTGCGCTCTCCGCCGCGCT AGCGCGGCGGAGAGCGCAG 895 TGCGCTCTCCGCCGCGCTCGAGCGCGGCGGAGAGCGCA 896 GCGCTCTCCGCCGCGCTCT AGAGCGCGGCGGAGAGCGC 897CGCTCTCCGCCGCGCTCTA TAGAGCGCGGCGGAGAGCG 898 GCTCTCCGCCGCGCTCTACGTAGAGCGCGGCGGAGAGC 899 CTCTCCGCCGCGCTCTACC GGTAGAGCGCGGCGGAGAG 900TCTCCGCCGCGCTCTACCT AGGTAGAGCGCGGCGGAGA 901 CTCCGCCGCGCTCTACCTCGAGGTAGAGCGCGGCGGAG 902 TCCGCCGCGCTCTACCTCC GGAGGTAGAGCGCGGCGGA 903CCGCCGCGCTCTACCTCCA TGGAGGTAGAGCGCGGCGG 904 CGCCGCGCTCTACCTCCATATGGAGGTAGAGCGCGGCG 905 GCCGCGCTCTACCTCCATT AATGGAGGTAGAGCGCGGC 906CCGCGCTCTACCTCCATTA TAATGGAGGTAGAGCGCGG 907 CGCGCTCTACCTCCATTAGCTAATGGAGGTAGAGCGCG 908 GCGCTCTACCTCCATTAGC GCTAATGGAGGTAGAGCGC 909CGCTCTACCTCCATTAGCC GGCTAATGGAGGTAGAGCG 910 GCTCTACCTCCATTAGCCGCGGCTAATGGAGGTAGAGC 911 CTCTACCTCCATTAGCCGC GCGGCTAATGGAGGTAGAG 912TCTACCTCCATTAGCCGCG CGCGGCTAATGGAGGTAGA 913 CTACCTCCATTAGCCGCGCGCGCGGCTAATGGAGGTAG 914 TACCTCCATTAGCCGCGCT AGCGCGGCTAATGGAGGTA 915ACCTCCATTAGCCGCGCTG CAGCGCGGCTAATGGAGGT 916 CCTCCATTAGCCGCGCTGCGCAGCGCGGCTAATGGAGG 917 CTCCATTAGCCGCGCTGCG CGCAGCGCGGCTAATGGAG 918TCCATTAGCCGCGCTGCGC GCGCAGCGCGGCTAATGGA 919 CCATTAGCCGCGCTGCGCGCGCGCAGCGCGGCTAATGG 920 CATTAGCCGCGCTGCGCGG CCGCGCAGCGCGGCTAATG 921ATTAGCCGCGCTGCGCGGT ACCGCGCAGCGCGGCTAAT 922 TTAGCCGCGCTGCGCGGTGCACCGCGCAGCGCGGCTAA 923 TAGCCGCGCTGCGCGGTGC GCACCGCGCAGCGCGGCTA 924AGCCGCGCTGCGCGGTGCT AGCACCGCGCAGCGCGGCT 925 GCCGCGCTGCGCGGTGCTGCAGCACCGCGCAGCGCGGC 926 CCGCGCTGCGCGGTGCTGC GCAGCACCGCGCAGCGCGG 927CGCGCTGCGCGGTGCTGCG CGCAGCACCGCGCAGCGCG 928 GCGCTGCGCGGTGCTGCGCGCGCAGCACCGCGCAGCGC 929 CGCTGCGCGGTGCTGCGCC GGCGCAGCACCGCGCAGCG 930GCTGCGCGGTGCTGCGCCC GGGCGCAGCACCGCGCAGC 931 CTGCGCGGTGCTGCGCCCTAGGGCGCAGCACCGCGCAG 932 TGCGCGGTGCTGCGCCCTC GAGGGCGCAGCACCGCGCA 933GCGCGGTGCTGCGCCCTCG CGAGGGCGCAGCACCGCGC 934 CGCGGTGCTGCGCCCTCGCGCGAGGGCGCAGCACCGCG 935 GCGGTGCTGCGCCCTCGCC GGCGAGGGCGCAGCACCGC 936CGGTGCTGCGCCCTCGCCG CGGCGAGGGCGCAGCACCG 937 GGTGCTGCGCCCTCGCCGGCCGGCGAGGGCGCAGCACC 938 GTGCTGCGCCCTCGCCGGT ACCGGCGAGGGCGCAGCAC 939TGCTGCGCCCTCGCCGGTG CACCGGCGAGGGCGCAGCA 940 GCTGCGCCCTCGCCGGTGCGCACCGGCGAGGGCGCAGC 941 CTGCGCCCTCGCCGGTGCC GGCACCGGCGAGGGCGCAG 942TGCGCCCTCGCCGGTGCCT AGGCACCGGCGAGGGCGCA 943 GCGCCCTCGCCGGTGCCTCGAGGCACCGGCGAGGGCGC 944 CGCCCTCGCCGGTGCCTCT AGAGGCACCGGCGAGGGCG 945GCCCTCGCCGGTGCCTCTC GAGAGGCACCGGCGAGGGC 946 CCCTCGCCGGTGCCTCTCTAGAGAGGCACCGGCGAGGG 947 CCTCGCCGGTGCCTCTCTC GAGAGAGGCACCGGCGAGG 948CTCGCCGGTGCCTCTCTCC GGAGAGAGGCACCGGCGAG 949 TCGCCGGTGCCTCTCTCCTAGGAGAGAGGCACCGGCGA 950 CGCCGGTGCCTCTCTCCTG CAGGAGAGAGGCACCGGCG 951GCCGGTGCCTCTCTCCTGG CCAGGAGAGAGGCACCGGC 952 CCGGTGCCTCTCTCCTGGGCCCAGGAGAGAGGCACCGG 953 CGGTGCCTCTCTCCTGGGT ACCCAGGAGAGAGGCACCG 954GGTGCCTCTCTCCTGGGTC GACCCAGGAGAGAGGCACC 955 GTGCCTCTCTCCTGGGTCCGGACCCAGGAGAGAGGCAC 956 TGCCTCTCTCCTGGGTCCC GGGACCCAGGAGAGAGGCA 957GCCTCTCTCCTGGGTCCCA TGGGACCCAGGAGAGAGGC 958 CCTCTCTCCTGGGTCCCAGCTGGGACCCAGGAGAGAGG 959 CTCTCTCCTGGGTCCCAGG CCTGGGACCCAGGAGAGAG 960TCTCTCCTGGGTCCCAGGA TCCTGGGACCCAGGAGAGA 961 CTCTCCTGGGTCCCAGGATATCCTGGGACCCAGGAGAG 962 TCTCCTGGGTCCCAGGATC GATCCTGGGACCCAGGAGA 963CTCCTGGGTCCCAGGATCG CGATCCTGGGACCCAGGAG 964 TCCTGGGTCCCAGGATCGGCCGATCCTGGGACCCAGGA 965 CCTGGGTCCCAGGATCGGC GCCGATCCTGGGACCCAGG 966CTGGGTCCCAGGATCGGCC GGCCGATCCTGGGACCCAG 967 TGGGTCCCAGGATCGGCCCGGGCCGATCCTGGGACCCA 968 GGGTCCCAGGATCGGCCCC GGGGCCGATCCTGGGACCC 969GGTCCCAGGATCGGCCCCC GGGGGCCGATCCTGGGACC 970 GTCCCAGGATCGGCCCCCATGGGGGCCGATCCTGGGAC 971 TCCCAGGATCGGCCCCCAC GTGGGGGCCGATCCTGGGA 972CCCAGGATCGGCCCCCACC GGTGGGGGCCGATCCTGGG 973 CCAGGATCGGCCCCCACCATGGTGGGGGCCGATCCTGG 974 CAGGATCGGCCCCCACCAT ATGGTGGGGGCCGATCCTG 975AGGATCGGCCCCCACCATC GATGGTGGGGGCCGATCCT 976 GGATCGGCCCCCACCATCCGGATGGTGGGGGCCGATCC 977 GATCGGCCCCCACCATCCA TGGATGGTGGGGGCCGATC 978ATCGGCCCCCACCATCCAG CTGGATGGTGGGGGCCGAT 979 TCGGCCCCCACCATCCAGGCCTGGATGGTGGGGGCCGA 980 CGGCCCCCACCATCCAGGC GCCTGGATGGTGGGGGCCG 981GGCCCCCACCATCCAGGCA TGCCTGGATGGTGGGGGCC 982 GCCCCCACCATCCAGGCACGTGCCTGGATGGTGGGGGC 983 CCCCCACCATCCAGGCACG CGTGCCTGGATGGTGGGGG 984CCCCACCATCCAGGCACGA TCGTGCCTGGATGGTGGGG 985 CCCACCATCCAGGCACGACGTCGTGCCTGGATGGTGGG 986 CCACCATCCAGGCACGACC GGTCGTGCCTGGATGGTGG 987CACCATCCAGGCACGACCC GGGTCGTGCCTGGATGGTG 988 ACCATCCAGGCACGACCCCGGGGTCGTGCCTGGATGGT 989 CCATCCAGGCACGACCCCC GGGGGTCGTGCCTGGATGG 990CATCCAGGCACGACCCCCT AGGGGGTCGTGCCTGGATG 991 ATCCAGGCACGACCCCCTTAAGGGGGTCGTGCCTGGAT 992 TCCAGGCACGACCCCCTTC GAAGGGGGTCGTGCCTGGA 993CCAGGCACGACCCCCTTCC GGAAGGGGGTCGTGCCTGG 994 CAGGCACGACCCCCTTCCCGGGAAGGGGGTCGTGCCTG 995 AGGCACGACCCCCTTCCCC GGGGAAGGGGGTCGTGCCT 996GGCACGACCCCCTTCCCCG CGGGGAAGGGGGTCGTGCC 997 GCACGACCCCCTTCCCCGGCCGGGGAAGGGGGTCGTGC 998 CACGACCCCCTTCCCCGGC GCCGGGGAAGGGGGTCGTG 999ACGACCCCCTTCCCCGGCC GGCCGGGGAAGGGGGTCGT 1000 CGACCCCCTTCCCCGGCCCGGGCCGGGGAAGGGGGTCG 1001 GACCCCCTTCCCCGGCCCC GGGGCCGGGGAAGGGGGTC 1002ACCCCCTTCCCCGGCCCCT AGGGGCCGGGGAAGGGGGT 1003 CCCCCTTCCCCGGCCCCTCGAGGGGCCGGGGAAGGGGG 1004 CCCCTTCCCCGGCCCCTCG CGAGGGGCCGGGGAAGGGG 1005CCCTTCCCCGGCCCCTCGG CCGAGGGGCCGGGGAAGGG 1006 CCTTCCCCGGCCCCTCGGCGCCGAGGGGCCGGGGAAGG 1007 CTTCCCCGGCCCCTCGGCC GGCCGAGGGGCCGGGGAAG 1008TTCCCCGGCCCCTCGGCCT AGGCCGAGGGGCCGGGGAA 1009 TCCCCGGCCCCTCGGCCTTAAGGCCGAGGGGCCGGGGA 1010 CCCCGGCCCCTCGGCCTTT AAAGGCCGAGGGGCCGGGG 1011CCCGGCCCCTCGGCCTTTC GAAAGGCCGAGGGGCCGGG 1012 CCGGCCCCTCGGCCTTTCCGGAAAGGCCGAGGGGCCGG 1013 CGGCCCCTCGGCCTTTCCC GGGAAAGGCCGAGGGGCCG 1014GGCCCCTCGGCCTTTCCCC GGGGAAAGGCCGAGGGGCC 1015 GCCCCTCGGCCTTTCCCCCGGGGGAAAGGCCGAGGGGC 1016 CCCCTCGGCCTTTCCCCCA TGGGGGAAAGGCCGAGGGG 1017CCCTCGGCCTTTCCCCCAA TTGGGGGAAAGGCCGAGGG 1018 CCTCGGCCTTTCCCCCAACGTTGGGGGAAAGGCCGAGG 1019 CTCGGCCTTTCCCCCAACT AGTTGGGGGAAAGGCCGAG 1020TCGGCCTTTCCCCCAACTC GAGTTGGGGGAAAGGCCGA 1021 CGGCCTTTCCCCCAACTCGCGAGTTGGGGGAAAGGCCG 1022 GGCCTTTCCCCCAACTCGG CCGAGTTGGGGGAAAGGCC 1023GCCTTTCCCCCAACTCGGC GCCGAGTTGGGGGAAAGGC 1024 CCTTTCCCCCAACTCGGCCGGCCGAGTTGGGGGAAAGG 1025 CTTTCCCCCAACTCGGCCA TGGCCGAGTTGGGGGAAAG 1026TTTCCCCCAACTCGGCCAT ATGGCCGAGTTGGGGGAAA 1027 TTCCCCCAACTCGGCCATCGATGGCCGAGTTGGGGGAA 1028 TCCCCCAACTCGGCCATCT AGATGGCCGAGTTGGGGGA 1029CCCCCAACTCGGCCATCTC GAGATGGCCGAGTTGGGGG 1030 CCCCAACTCGGCCATCTCCGGAGATGGCCGAGTTGGGG 1031 CCCAACTCGGCCATCTCCG CGGAGATGGCCGAGTTGGG 1032CCAACTCGGCCATCTCCGA TCGGAGATGGCCGAGTTGG 1033 CAACTCGGCCATCTCCGACGTCGGAGATGGCCGAGTTG 1034 AACTCGGCCATCTCCGACC GGTCGGAGATGGCCGAGTT 1035ACTCGGCCATCTCCGACCC GGGTCGGAGATGGCCGAGT 1036 CTCGGCCATCTCCGACCCGCGGGTCGGAGATGGCCGAG 1037 TCGGCCATCTCCGACCCGG CCGGGTCGGAGATGGCCGA 1038CGGCCATCTCCGACCCGGG CCCGGGTCGGAGATGGCCG 1039 GGCCATCTCCGACCCGGGGCCCCGGGTCGGAGATGGCC 1040 GCCATCTCCGACCCGGGGC GCCCCGGGTCGGAGATGGC 1041CCATCTCCGACCCGGGGCG CGCCCCGGGTCGGAGATGG 1042 CATCTCCGACCCGGGGCGCGCGCCCCGGGTCGGAGATG 1043 ATCTCCGACCCGGGGCGCG CGCGCCCCGGGTCGGAGAT 1044TCTCCGACCCGGGGCGCGT ACGCGCCCCGGGTCGGAGA 1045 CTCCGACCCGGGGCGCGTGCACGCGCCCCGGGTCGGAG 1046 TCCGACCCGGGGCGCGTGT ACACGCGCCCCGGGTCGGA 1047CCGACCCGGGGCGCGTGTT AACACGCGCCCCGGGTCGG 1048 CGACCCGGGGCGCGTGTTCGAACACGCGCCCCGGGTCG 1049 GACCCGGGGCGCGTGTTCC GGAACACGCGCCCCGGGTC 1050ACCCGGGGCGCGTGTTCCC GGGAACACGCGCCCCGGGT 1051 CCCGGGGCGCGTGTTCCCCGGGGAACACGCGCCCCGGG 1052 CCGGGGCGCGTGTTCCCCC GGGGGAACACGCGCCCCGG 1053CGGGGCGCGTGTTCCCCCC GGGGGGAACACGCGCCCCG 1054 GGGGCGCGTGTTCCCCCCGCGGGGGGAACACGCGCCCC 1055 GGGCGCGTGTTCCCCCCGG CCGGGGGGAACACGCGCCC 1056GGCGCGTGTTCCCCCCGGC GCCGGGGGGAACACGCGCC 1057 GCGCGTGTTCCCCCCGGCCGGCCGGGGGGAACACGCGC 1058 CGCGTGTTCCCCCCGGCCC GGGCCGGGGGGAACACGCG 1059GCGTGTTCCCCCCGGCCCG CGGGCCGGGGGGAACACGC 1060 CGTGTTCCCCCCGGCCCGGCCGGGCCGGGGGGAACACG 1061 GTGTTCCCCCCGGCCCGGC GCCGGGCCGGGGGGAACAC 1062TGTTCCCCCCGGCCCGGCG CGCCGGGCCGGGGGGAACA 1063 GTTCCCCCCGGCCCGGCGCGCGCCGGGCCGGGGGGAAC 1064 TTCCCCCCGGCCCGGCGCC GGCGCCGGGCCGGGGGGAA 1065TCCCCCCGGCCCGGCGCCT AGGCGCCGGGCCGGGGGGA 1066 CCCCCCGGCCCGGCGCCTTAAGGCGCCGGGCCGGGGGG 1067 CCCCCGGCCCGGCGCCTTC GAAGGCGCCGGGCCGGGGG 1068CCCCGGCCCGGCGCCTTCT AGAAGGCGCCGGGCCGGGG 1069 CCCGGCCCGGCGCCTTCTCGAGAAGGCGCCGGGCCGGG 1070 CCGGCCCGGCGCCTTCTCT AGAGAAGGCGCCGGGCCGG 1071CGGCCCGGCGCCTTCTCTC GAGAGAAGGCGCCGGGCCG 1072 GGCCCGGCGCCTTCTCTCCGGAGAGAAGGCGCCGGGCC 1073 GCCCGGCGCCTTCTCTCCC GGGAGAGAAGGCGCCGGGC 1074CCCGGCGCCTTCTCTCCCT AGGGAGAGAAGGCGCCGGG 1075 CCGGCGCCTTCTCTCCCTCGAGGGAGAGAAGGCGCCGG 1076 CGGCGCCTTCTCTCCCTCC GGAGGGAGAGAAGGCGCCG 1077GGCGCCTTCTCTCCCTCCG CGGAGGGAGAGAAGGCGCC 1078 GCGCCTTCTCTCCCTCCGGCCGGAGGGAGAGAAGGCGC 1079 CGCCTTCTCTCCCTCCGGG CCCGGAGGGAGAGAAGGCG 1080GCCTTCTCTCCCTCCGGGG CCCCGGAGGGAGAGAAGGC 1081 CCTTCTCTCCCTCCGGGGGCCCCCGGAGGGAGAGAAGG 1082 CTTCTCTCCCTCCGGGGGC GCCCCCGGAGGGAGAGAAG 1083TTCTCTCCCTCCGGGGGCA TGCCCCCGGAGGGAGAGAA 1084 TCTCTCCCTCCGGGGGCACGTGCCCCCGGAGGGAGAGA 1085 CTCTCCCTCCGGGGGCACC GGTGCCCCCGGAGGGAGAG 1086TCTCCCTCCGGGGGCACCC GGGTGCCCCCGGAGGGAGA 1087 CTCCCTCCGGGGGCACCCGCGGGTGCCCCCGGAGGGAG 1088 TCCCTCCGGGGGCACCCGC GCGGGTGCCCCCGGAGGGA 1089CCCTCCGGGGGCACCCGCT AGCGGGTGCCCCCGGAGGG 1090 CCTCCGGGGGCACCCGCTCGAGCGGGTGCCCCCGGAGG 1091 CTCCGGGGGCACCCGCTCC GGAGCGGGTGCCCCCGGAG 1092TCCGGGGGCACCCGCTCCC GGGAGCGGGTGCCCCCGGA 1093 CCGGGGGCACCCGCTCCCTAGGGAGCGGGTGCCCCCGG 1094 CGGGGGCACCCGCTCCCTA TAGGGAGCGGGTGCCCCCG 1095GGGGGCACCCGCTCCCTAG CTAGGGAGCGGGTGCCCCC 1096 GGGGCACCCGCTCCCTAGCGCTAGGGAGCGGGTGCCCC 1097 GGGCACCCGCTCCCTAGCC GGCTAGGGAGCGGGTGCCC 1098GGCACCCGCTCCCTAGCCC GGGCTAGGGAGCGGGTGCC 1099 GCACCCGCTCCCTAGCCCCGGGGCTAGGGAGCGGGTGC 1100 CACCCGCTCCCTAGCCCCG CGGGGCTAGGGAGCGGGTG 1101ACCCGCTCCCTAGCCCCGG CCGGGGCTAGGGAGCGGGT 1102 CCCGCTCCCTAGCCCCGGCGCCGGGGCTAGGGAGCGGG 1103 CCGCTCCCTAGCCCCGGCC GGCCGGGGCTAGGGAGCGG 1104CGCTCCCTAGCCCCGGCCC GGGCCGGGGCTAGGGAGCG 1105 GCTCCCTAGCCCCGGCCCGCGGGCCGGGGCTAGGGAGC 1106 CTCCCTAGCCCCGGCCCGG CCGGGCCGGGGCTAGGGAG 1107TCCCTAGCCCCGGCCCGGC GCCGGGCCGGGGCTAGGGA 1108 CCCTAGCCCCGGCCCGGCCGGCCGGGCCGGGGCTAGGG 1109 CCTAGCCCCGGCCCGGCCC GGGCCGGGCCGGGGCTAGG 1110CTAGCCCCGGCCCGGCCCT AGGGCCGGGCCGGGGCTAG 1111 TAGCCCCGGCCCGGCCCTCGAGGGCCGGGCCGGGGCTA 1112 AGCCCCGGCCCGGCCCTCC GGAGGGCCGGGCCGGGGCT 1113GCCCCGGCCCGGCCCTCCC GGGAGGGCCGGGCCGGGGC 1114 CCCCGGCCCGGCCCTCCCCGGGGAGGGCCGGGCCGGGG 1115 CCCGGCCCGGCCCTCCCCG CGGGGAGGGCCGGGCCGGG 1116CCGGCCCGGCCCTCCCCGC GCGGGGAGGGCCGGGCCGG 1117 CGGCCCGGCCCTCCCCGCGCGCGGGGAGGGCCGGGCCG 1118 GGCCCGGCCCTCCCCGCGG CCGCGGGGAGGGCCGGGCC 1119GCCCGGCCCTCCCCGCGGC GCCGCGGGGAGGGCCGGGC 1120 CCCGGCCCTCCCCGCGGCGCGCCGCGGGGAGGGCCGGG 1121 CCGGCCCTCCCCGCGGCGC GCGCCGCGGGGAGGGCCGG 1122CGGCCCTCCCCGCGGCGCA TGCGCCGCGGGGAGGGCCG 1123 GGCCCTCCCCGCGGCGCAGCTGCGCCGCGGGGAGGGCC 1124 GCCCTCCCCGCGGCGCAGC GCTGCGCCGCGGGGAGGGC 1125CCCTCCCCGCGGCGCAGCA TGCTGCGCCGCGGGGAGGG 1126 CCTCCCCGCGGCGCAGCACGTGCTGCGCCGCGGGGAGG 1127 CTCCCCGCGGCGCAGCACG CGTGCTGCGCCGCGGGGAG 1128TCCCCGCGGCGCAGCACGG CCGTGCTGCGCCGCGGGGA 1129 CCCCGCGGCGCAGCACGGATCCGTGCTGCGCCGCGGGG 1130 CCCGCGGCGCAGCACGGAG CTCCGTGCTGCGCCGCGGG 1131CCGCGGCGCAGCACGGAGT ACTCCGTGCTGCGCCGCGG 1132 CGCGGCGCAGCACGGAGTCGACTCCGTGCTGCGCCGCG 1133 GCGGCGCAGCACGGAGTCT AGACTCCGTGCTGCGCCGC 1134CGGCGCAGCACGGAGTCTC GAGACTCCGTGCTGCGCCG 1135 GGCGCAGCACGGAGTCTCGCGAGACTCCGTGCTGCGCC 1136 GCGCAGCACGGAGTCTCGG CCGAGACTCCGTGCTGCGC 1137CGCAGCACGGAGTCTCGGC GCCGAGACTCCGTGCTGCG 1138 GCAGCACGGAGTCTCGGCGCGCCGAGACTCCGTGCTGC 1139 CAGCACGGAGTCTCGGCGT ACGCCGAGACTCCGTGCTG 1140AGCACGGAGTCTCGGCGTC GACGCCGAGACTCCGTGCT 1141 GCACGGAGTCTCGGCGTCCGGACGCCGAGACTCCGTGC 1142 CACGGAGTCTCGGCGTCCC GGGACGCCGAGACTCCGTG 1143ACGGAGTCTCGGCGTCCCA TGGGACGCCGAGACTCCGT 1144 CGGAGTCTCGGCGTCCCATATGGGACGCCGAGACTCCG 1145 GGAGTCTCGGCGTCCCATG CATGGGACGCCGAGACTCC 1146GAGTCTCGGCGTCCCATGG CCATGGGACGCCGAGACTC 1147 AGTCTCGGCGTCCCATGGCGCCATGGGACGCCGAGACT 1148 GTCTCGGCGTCCCATGGCG CGCCATGGGACGCCGAGAC 1149TCTCGGCGTCCCATGGCGC GCGCCATGGGACGCCGAGA 1150 CTCGGCGTCCCATGGCGCATGCGCCATGGGACGCCGAG 1151 TCGGCGTCCCATGGCGCAA TTGCGCCATGGGACGCCGA 1152CGGCGTCCCATGGCGCAAC GTTGCGCCATGGGACGCCG 1153 GGCGTCCCATGGCGCAACCGGTTGCGCCATGGGACGCC 1154 GCGTCCCATGGCGCAACCT AGGTTGCGCCATGGGACGC 1155CGTCCCATGGCGCAACCTA TAGGTTGCGCCATGGGACG 1156 GTCCCATGGCGCAACCTACGTAGGTTGCGCCATGGGAC 1157 TCCCATGGCGCAACCTACG CGTAGGTTGCGCCATGGGA 1158CCCATGGCGCAACCTACGG CCGTAGGTTGCGCCATGGG 1159 CCATGGCGCAACCTACGGCGCCGTAGGTTGCGCCATGG 1160 CATGGCGCAACCTACGGCC GGCCGTAGGTTGCGCCATG 1161ATGGCGCAACCTACGGCCT AGGCCGTAGGTTGCGCCAT 1162 TGGCGCAACCTACGGCCTCGAGGCCGTAGGTTGCGCCA 1163 GGCGCAACCTACGGCCTCG CGAGGCCGTAGGTTGCGCC 1164GCGCAACCTACGGCCTCGG CCGAGGCCGTAGGTTGCGC 1165 CGCAACCTACGGCCTCGGCGCCGAGGCCGTAGGTTGCG 1166 GCAACCTACGGCCTCGGCC GGCCGAGGCCGTAGGTTGC 1167CAACCTACGGCCTCGGCCC GGGCCGAGGCCGTAGGTTG 1168 AACCTACGGCCTCGGCCCATGGGCCGAGGCCGTAGGTT 1169 ACCTACGGCCTCGGCCCAG CTGGGCCGAGGCCGTAGGT 1170CCTACGGCCTCGGCCCAGA TCTGGGCCGAGGCCGTAGG 1171 CTACGGCCTCGGCCCAGAATTCTGGGCCGAGGCCGTAG 1172 TACGGCCTCGGCCCAGAAG CTTCTGGGCCGAGGCCGTA 1173ACGGCCTCGGCCCAGAAGC GCTTCTGGGCCGAGGCCGT 1174 CGGCCTCGGCCCAGAAGCTAGCTTCTGGGCCGAGGCCG 1175 GGCCTCGGCCCAGAAGCTG CAGCTTCTGGGCCGAGGCC 1176GCCTCGGCCCAGAAGCTGG CCAGCTTCTGGGCCGAGGC 1177 CCTCGGCCCAGAAGCTGGTACCAGCTTCTGGGCCGAGG 1178 CTCGGCCCAGAAGCTGGTG CACCAGCTTCTGGGCCGAG 1179TCGGCCCAGAAGCTGGTGC GCACCAGCTTCTGGGCCGA 1180 CGGCCCAGAAGCTGGTGCGCGCACCAGCTTCTGGGCCG 1181 GGCCCAGAAGCTGGTGCGG CCGCACCAGCTTCTGGGCC 1182GCCCAGAAGCTGGTGCGGC GCCGCACCAGCTTCTGGGC 1183 CCCAGAAGCTGGTGCGGCCGGCCGCACCAGCTTCTGGG 1184 CCAGAAGCTGGTGCGGCCG CGGCCGCACCAGCTTCTGG 1185CAGAAGCTGGTGCGGCCGA TCGGCCGCACCAGCTTCTG 1186 AGAAGCTGGTGCGGCCGATATCGGCCGCACCAGCTTCT 1187 GAAGCTGGTGCGGCCGATC GATCGGCCGCACCAGCTTC 1188AAGCTGGTGCGGCCGATCC GGATCGGCCGCACCAGCTT 1189 AGCTGGTGCGGCCGATCCGCGGATCGGCCGCACCAGCT 1190 GCTGGTGCGGCCGATCCGC GCGGATCGGCCGCACCAGC 1191CTGGTGCGGCCGATCCGCG CGCGGATCGGCCGCACCAG 1192 TGGTGCGGCCGATCCGCGCGCGCGGATCGGCCGCACCA 1193 GGTGCGGCCGATCCGCGCC GGCGCGGATCGGCCGCACC 1194GTGCGGCCGATCCGCGCCG CGGCGCGGATCGGCCGCAC 1195 TGCGGCCGATCCGCGCCGTACGGCGCGGATCGGCCGCA 1196 GCGGCCGATCCGCGCCGTG CACGGCGCGGATCGGCCGC 1197CGGCCGATCCGCGCCGTGT ACACGGCGCGGATCGGCCG 1198 GGCCGATCCGCGCCGTGTGCACACGGCGCGGATCGGCC 1199 GCCGATCCGCGCCGTGTGC GCACACGGCGCGGATCGGC 1200CCGATCCGCGCCGTGTGCC GGCACACGGCGCGGATCGG 1201 CGATCCGCGCCGTGTGCCGCGGCACACGGCGCGGATCG 1202 GATCCGCGCCGTGTGCCGC GCGGCACACGGCGCGGATC 1203ATCCGCGCCGTGTGCCGCA TGCGGCACACGGCGCGGAT 1204 TCCGCGCCGTGTGCCGCATATGCGGCACACGGCGCGGA 1205 CCGCGCCGTGTGCCGCATC GATGCGGCACACGGCGCGG 1206CGCGCCGTGTGCCGCATCC GGATGCGGCACACGGCGCG 1207 GCGCCGTGTGCCGCATCCTAGGATGCGGCACACGGCGC 1208 CGCCGTGTGCCGCATCCTG CAGGATGCGGCACACGGCG 1209GCCGTGTGCCGCATCCTGC GCAGGATGCGGCACACGGC 1210 CCGTGTGCCGCATCCTGCATGCAGGATGCGGCACACGG 1211 CGTGTGCCGCATCCTGCAG CTGCAGGATGCGGCACACG 1212GTGTGCCGCATCCTGCAGA TCTGCAGGATGCGGCACAC 1213 TGTGCCGCATCCTGCAGATATCTGCAGGATGCGGCACA 1214 GTGCCGCATCCTGCAGATC GATCTGCAGGATGCGGCAC 1215TGCCGCATCCTGCAGATCC GGATCTGCAGGATGCGGCA 1216 GCCGCATCCTGCAGATCCCGGGATCTGCAGGATGCGGC 1217 CCGCATCCTGCAGATCCCG CGGGATCTGCAGGATGCGG 1218CGCATCCTGCAGATCCCGG CCGGGATCTGCAGGATGCG 1219 GCATCCTGCAGATCCCGGATCCGGGATCTGCAGGATGC 1220 CATCCTGCAGATCCCGGAG CTCCGGGATCTGCAGGATG 1221ATCCTGCAGATCCCGGAGT ACTCCGGGATCTGCAGGAT 1222 TCCTGCAGATCCCGGAGTCGACTCCGGGATCTGCAGGA 1223 CCTGCAGATCCCGGAGTCC GGACTCCGGGATCTGCAGG 1224CTGCAGATCCCGGAGTCCG CGGACTCCGGGATCTGCAG 1225 TGCAGATCCCGGAGTCCGATCGGACTCCGGGATCTGCA 1226 GCAGATCCCGGAGTCCGAC GTCGGACTCCGGGATCTGC 1227CAGATCCCGGAGTCCGACC GGTCGGACTCCGGGATCTG 1228 AGATCCCGGAGTCCGACCCGGGTCGGACTCCGGGATCT 1229 GATCCCGGAGTCCGACCCC GGGGTCGGACTCCGGGATC 1230ATCCCGGAGTCCGACCCCT AGGGGTCGGACTCCGGGAT 1231 TCCCGGAGTCCGACCCCTCGAGGGGTCGGACTCCGGGA 1232 CCCGGAGTCCGACCCCTCC GGAGGGGTCGGACTCCGGG 1233CCGGAGTCCGACCCCTCCA TGGAGGGGTCGGACTCCGG 1234 CGGAGTCCGACCCCTCCAATTGGAGGGGTCGGACTCCG 1235 GGAGTCCGACCCCTCCAAC GTTGGAGGGGTCGGACTCC 1236GAGTCCGACCCCTCCAACC GGTTGGAGGGGTCGGACTC 1237 AGTCCGACCCCTCCAACCTAGGTTGGAGGGGTCGGACT 1238 GTCCGACCCCTCCAACCTG CAGGTTGGAGGGGTCGGAC 1239TCCGACCCCTCCAACCTGC GCAGGTTGGAGGGGTCGGA 1240 CCGACCCCTCCAACCTGCGCGCAGGTTGGAGGGGTCGG 1241 CGACCCCTCCAACCTGCGG CCGCAGGTTGGAGGGGTCG 1242GACCCCTCCAACCTGCGGC GCCGCAGGTTGGAGGGGTC 1243 ACCCCTCCAACCTGCGGCCGGCCGCAGGTTGGAGGGGT 1244 CCCCTCCAACCTGCGGCCC GGGCCGCAGGTTGGAGGGG 1245CCCTCCAACCTGCGGCCCT AGGGCCGCAGGTTGGAGGG 1246 CCTCCAACCTGCGGCCCTATAGGGCCGCAGGTTGGAGG 1247 CTCCAACCTGCGGCCCTAG CTAGGGCCGCAGGTTGGAG 1248TCCAACCTGCGGCCCTAGA TCTAGGGCCGCAGGTTGGA 1249 CCAACCTGCGGCCCTAGAGCTCTAGGGCCGCAGGTTGG 1250 CAACCTGCGGCCCTAGAGC GCTCTAGGGCCGCAGGTTG 1251AACCTGCGGCCCTAGAGCG CGCTCTAGGGCCGCAGGTT 1252 ACCTGCGGCCCTAGAGCGCGCGCTCTAGGGCCGCAGGT 1253 CCTGCGGCCCTAGAGCGCC GGCGCTCTAGGGCCGCAGG 1254CTGCGGCCCTAGAGCGCCC GGGCGCTCTAGGGCCGCAG 1255 TGCGGCCCTAGAGCGCCCCGGGGCGCTCTAGGGCCGCA 1256 GCGGCCCTAGAGCGCCCCC GGGGGCGCTCTAGGGCCGC 1257CGGCCCTAGAGCGCCCCCG CGGGGGCGCTCTAGGGCCG 1258 GGCCCTAGAGCGCCCCCGCGCGGGGGCGCTCTAGGGCC 1259 GCCCTAGAGCGCCCCCGCC GGCGGGGGCGCTCTAGGGC 1260CCCTAGAGCGCCCCCGCCG CGGCGGGGGCGCTCTAGGG 1261 CCTAGAGCGCCCCCGCCGCGCGGCGGGGGCGCTCTAGG 1262 CTAGAGCGCCCCCGCCGCC GGCGGCGGGGGCGCTCTAG 1263TAGAGCGCCCCCGCCGCCC GGGCGGCGGGGGCGCTCTA 1264 AGAGCGCCCCCGCCGCCCCGGGGCGGCGGGGGCGCTCT 1265 GAGCGCCCCCGCCGCCCCG CGGGGCGGCGGGGGCGCTC 1266AGCGCCCCCGCCGCCCCGG CCGGGGCGGCGGGGGCGCT 1267 GCGCCCCCGCCGCCCCGGGCCCGGGGCGGCGGGGGCGC 1268 CGCCCCCGCCGCCCCGGGG CCCCGGGGCGGCGGGGGCG 1269GCCCCCGCCGCCCCGGGGG CCCCCGGGGCGGCGGGGGC 1270 CCCCCGCCGCCCCGGGGGATCCCCCGGGGCGGCGGGGG 1271 CCCCGCCGCCCCGGGGGAA TTCCCCCGGGGCGGCGGGG 1272CCCGCCGCCCCGGGGGAAG CTTCCCCCGGGGCGGCGGG 1273 CCGCCGCCCCGGGGGAAGGCCTTCCCCCGGGGCGGCGG 1274 CGCCGCCCCGGGGGAAGGA TCCTTCCCCCGGGGCGGCG 1275GCCGCCCCGGGGGAAGGAG CTCCTTCCCCCGGGGCGGC 1276 CCGCCCCGGGGGAAGGAGATCTCCTTCCCCCGGGGCGG 1277 CGCCCCGGGGGAAGGAGAG CTCTCCTTCCCCCGGGGCG 1278GCCCCGGGGGAAGGAGAGC GCTCTCCTTCCCCCGGGGC 1279 CCCCGGGGGAAGGAGAGCGCGCTCTCCTTCCCCCGGGG 1280 CCCGGGGGAAGGAGAGCGC GCGCTCTCCTTCCCCCGGG 1281CCGGGGGAAGGAGAGCGCG CGCGCTCTCCTTCCCCCGG 1282 CGGGGGAAGGAGAGCGCGATCGCGCTCTCCTTCCCCCG 1283 GGGGGAAGGAGAGCGCGAG CTCGCGCTCTCCTTCCCCC 1284GGGGAAGGAGAGCGCGAGC GCTCGCGCTCTCCTTCCCC 1285 GGGAAGGAGAGCGCGAGCGCGCTCGCGCTCTCCTTCCC 1286 GGAAGGAGAGCGCGAGCGC GCGCTCGCGCTCTCCTTCC 1287GAAGGAGAGCGCGAGCGCG CGCGCTCGCGCTCTCCTTC 1288 AAGGAGAGCGCGAGCGCGCGCGCGCTCGCGCTCTCCTT 1289 AGGAGAGCGCGAGCGCGCT AGCGCGCTCGCGCTCTCCT 1290GGAGAGCGCGAGCGCGCTG CAGCGCGCTCGCGCTCTCC 1291 GAGAGCGCGAGCGCGCTGATCAGCGCGCTCGCGCTCTC 1292 AGAGCGCGAGCGCGCTGAG CTCAGCGCGCTCGCGCTCT 1293GAGCGCGAGCGCGCTGAGC GCTCAGCGCGCTCGCGCTC 1294 AGCGCGAGCGCGCTGAGCATGCTCAGCGCGCTCGCGCT 1295 GCGCGAGCGCGCTGAGCAG CTGCTCAGCGCGCTCGCGC 1296CGCGAGCGCGCTGAGCAGA TCTGCTCAGCGCGCTCGCG 1297 GCGAGCGCGCTGAGCAGACGTCTGCTCAGCGCGCTCGC 1298 CGAGCGCGCTGAGCAGACA TGTCTGCTCAGCGCGCTCG 1299GAGCGCGCTGAGCAGACAG CTGTCTGCTCAGCGCGCTC 1300 AGCGCGCTGAGCAGACAGATCTGTCTGCTCAGCGCGCT 1301 GCGCGCTGAGCAGACAGAG CTCTGTCTGCTCAGCGCGC 1302CGCGCTGAGCAGACAGAGC GCTCTGTCTGCTCAGCGCG 1303 GCGCTGAGCAGACAGAGCGCGCTCTGTCTGCTCAGCGC 1304 CGCTGAGCAGACAGAGCGG CCGCTCTGTCTGCTCAGCG 1305GCTGAGCAGACAGAGCGGG CCCGCTCTGTCTGCTCAGC 1306 CTGAGCAGACAGAGCGGGATCCCGCTCTGTCTGCTCAG 1307 TGAGCAGACAGAGCGGGAG CTCCCGCTCTGTCTGCTCA 1308GAGCAGACAGAGCGGGAGA TCTCCCGCTCTGTCTGCTC 1309 AGCAGACAGAGCGGGAGAATTCTCCCGCTCTGTCTGCT 1310 GCAGACAGAGCGGGAGAAC GTTCTCCCGCTCTGTCTGC 1311CAGACAGAGCGGGAGAACG CGTTCTCCCGCTCTGTCTG 1312 AGACAGAGCGGGAGAACGCGCGTTCTCCCGCTCTGTCT 1313 GACAGAGCGGGAGAACGCG CGCGTTCTCCCGCTCTGTC 1314ACAGAGCGGGAGAACGCGT ACGCGTTCTCCCGCTCTGT 1315 CAGAGCGGGAGAACGCGTCGACGCGTTCTCCCGCTCTG 1316 AGAGCGGGAGAACGCGTCC GGACGCGTTCTCCCGCTCT 1317GAGCGGGAGAACGCGTCCT AGGACGCGTTCTCCCGCTC 1318 AGCGGGAGAACGCGTCCTCGAGGACGCGTTCTCCCGCT 1319 GCGGGAGAACGCGTCCTCG CGAGGACGCGTTCTCCCGC 1320CGGGAGAACGCGTCCTCGC GCGAGGACGCGTTCTCCCG 1321 GGGAGAACGCGTCCTCGCCGGCGAGGACGCGTTCTCCC 1322 GGAGAACGCGTCCTCGCCC GGGCGAGGACGCGTTCTCC 1323GAGAACGCGTCCTCGCCCG CGGGCGAGGACGCGTTCTC 1324 AGAACGCGTCCTCGCCCGCGCGGGCGAGGACGCGTTCT 1325 GAACGCGTCCTCGCCCGCC GGCGGGCGAGGACGCGTTC 1326AACGCGTCCTCGCCCGCCG CGGCGGGCGAGGACGCGTT 1327 ACGCGTCCTCGCCCGCCGGCCGGCGGGCGAGGACGCGT 1328 CGCGTCCTCGCCCGCCGGC GCCGGCGGGCGAGGACGCG 1329GCGTCCTCGCCCGCCGGCC GGCCGGCGGGCGAGGACGC 1330 CGTCCTCGCCCGCCGGCCGCGGCCGGCGGGCGAGGACG 1331 GTCCTCGCCCGCCGGCCGG CCGGCCGGCGGGCGAGGAC 1332TCCTCGCCCGCCGGCCGGG CCCGGCCGGCGGGCGAGGA 1333 CCTCGCCCGCCGGCCGGGATCCCGGCCGGCGGGCGAGG 1334 CTCGCCCGCCGGCCGGGAG CTCCCGGCCGGCGGGCGAG 1335TCGCCCGCCGGCCGGGAGG CCTCCCGGCCGGCGGGCGA 1336 CGCCCGCCGGCCGGGAGGCGCCTCCCGGCCGGCGGGCG 1337 GCCCGCCGGCCGGGAGGCC GGCCTCCCGGCCGGCGGGC 1338CCCGCCGGCCGGGAGGCCC GGGCCTCCCGGCCGGCGGG 1339 CCGCCGGCCGGGAGGCCCCGGGGCCTCCCGGCCGGCGG 1340 CGCCGGCCGGGAGGCCCCG CGGGGCCTCCCGGCCGGCG 1341GCCGGCCGGGAGGCCCCGG CCGGGGCCTCCCGGCCGGC 1342 CCGGCCGGGAGGCCCCGGATCCGGGGCCTCCCGGCCGG 1343 CGGCCGGGAGGCCCCGGAG CTCCGGGGCCTCCCGGCCG 1344GGCCGGGAGGCCCCGGAGC GCTCCGGGGCCTCCCGGCC 1345 GCCGGGAGGCCCCGGAGCTAGCTCCGGGGCCTCCCGGC 1346 CCGGGAGGCCCCGGAGCTG CAGCTCCGGGGCCTCCCGG 1347CGGGAGGCCCCGGAGCTGG CCAGCTCCGGGGCCTCCCG 1348 GGGAGGCCCCGGAGCTGGCGCCAGCTCCGGGGCCTCCC 1349 GGAGGCCCCGGAGCTGGCC GGCCAGCTCCGGGGCCTCC 1350GAGGCCCCGGAGCTGGCCC GGGCCAGCTCCGGGGCCTC 1351 AGGCCCCGGAGCTGGCCCATGGGCCAGCTCCGGGGCCT 1352 GGCCCCGGAGCTGGCCCAT ATGGGCCAGCTCCGGGGCC 1353GCCCCGGAGCTGGCCCATG CATGGGCCAGCTCCGGGGC 1354 CCCCGGAGCTGGCCCATGGCCATGGGCCAGCTCCGGGG 1355 CCCGGAGCTGGCCCATGGG CCCATGGGCCAGCTCCGGG 1356CCGGAGCTGGCCCATGGGG CCCCATGGGCCAGCTCCGG 1357 CGGAGCTGGCCCATGGGGATCCCCATGGGCCAGCTCCG 1358 GGAGCTGGCCCATGGGGAG CTCCCCATGGGCCAGCTCC 1359GAGCTGGCCCATGGGGAGC GCTCCCCATGGGCCAGCTC 1360 AGCTGGCCCATGGGGAGCATGCTCCCCATGGGCCAGCT 1361 GCTGGCCCATGGGGAGCAG CTGCTCCCCATGGGCCAGC 1362CTGGCCCATGGGGAGCAGG CCTGCTCCCCATGGGCCAG 1363 TGGCCCATGGGGAGCAGGCGCCTGCTCCCCATGGGCCA 1364 GGCCCATGGGGAGCAGGCG CGCCTGCTCCCCATGGGCC 1365GCCCATGGGGAGCAGGCGC GCGCCTGCTCCCCATGGGC 1366 CCCATGGGGAGCAGGCGCCGGCGCCTGCTCCCCATGGG 1367 CCATGGGGAGCAGGCGCCC GGGCGCCTGCTCCCCATGG 1368CATGGGGAGCAGGCGCCCG CGGGCGCCTGCTCCCCATG 1369 ATGGGGAGCAGGCGCCCGGCCGGGCGCCTGCTCCCCAT 1370 TGGGGAGCAGGCGCCCGGT ACCGGGCGCCTGCTCCCCA 1371GGGGAGCAGGCGCCCGGTG CACCGGGCGCCTGCTCCCC 1372 GGGAGCAGGCGCCCGGTGCGCACCGGGCGCCTGCTCCC 1373 GGAGCAGGCGCCCGGTGCC GGCACCGGGCGCCTGCTCC 1374GAGCAGGCGCCCGGTGCCG CGGCACCGGGCGCCTGCTC 1375 AGCAGGCGCCCGGTGCCGGCCGGCACCGGGCGCCTGCT 1376 GCAGGCGCCCGGTGCCGGC GCCGGCACCGGGCGCCTGC 1377CAGGCGCCCGGTGCCGGCC GGCCGGCACCGGGCGCCTG 1378 AGGCGCCCGGTGCCGGCCATGGCCGGCACCGGGCGCCT 1379 GGCGCCCGGTGCCGGCCAC GTGGCCGGCACCGGGCGCC 1380GCGCCCGGTGCCGGCCACG CGTGGCCGGCACCGGGCGC 1381 CGCCCGGTGCCGGCCACGATCGTGGCCGGCACCGGGCG 1382 GCCCGGTGCCGGCCACGAC GTCGTGGCCGGCACCGGGC 1383CCCGGTGCCGGCCACGACG CGTCGTGGCCGGCACCGGG 1384 CCGGTGCCGGCCACGACGATCGTCGTGGCCGGCACCGG 1385 CGGTGCCGGCCACGACGAC GTCGTCGTGGCCGGCACCG 1386GGTGCCGGCCACGACGACC GGTCGTCGTGGCCGGCACC 1387 GTGCCGGCCACGACGACCGCGGTCGTCGTGGCCGGCAC 1388 TGCCGGCCACGACGACCGC GCGGTCGTCGTGGCCGGCA 1389GCCGGCCACGACGACCGCC GGCGGTCGTCGTGGCCGGC 1390 CCGGCCACGACGACCGCCATGGCGGTCGTCGTGGCCGG 1391 CGGCCACGACGACCGCCAC GTGGCGGTCGTCGTGGCCG 1392GGCCACGACGACCGCCACC GGTGGCGGTCGTCGTGGCC 1393 GCCACGACGACCGCCACCGCGGTGGCGGTCGTCGTGGC 1394 CCACGACGACCGCCACCGC GCGGTGGCGGTCGTCGTGG 1395CACGACGACCGCCACCGCC GGCGGTGGCGGTCGTCGTG 1396 ACGACGACCGCCACCGCCCGGGCGGTGGCGGTCGTCGT 1397 CGACGACCGCCACCGCCCG CGGGCGGTGGCGGTCGTCG 1398GACGACCGCCACCGCCCGC GCGGGCGGTGGCGGTCGTC 1399 ACGACCGCCACCGCCCGCGCGCGGGCGGTGGCGGTCGT 1400 CGACCGCCACCGCCCGCGC GCGCGGGCGGTGGCGGTCG 1401GACCGCCACCGCCCGCGCC GGCGCGGGCGGTGGCGGTC 1402 ACCGCCACCGCCCGCGCCGCGGCGCGGGCGGTGGCGGT 1403 CCGCCACCGCCCGCGCCGC GCGGCGCGGGCGGTGGCGG 1404CGCCACCGCCCGCGCCGCG CGCGGCGCGGGCGGTGGCG 1405 GCCACCGCCCGCGCCGCGATCGCGGCGCGGGCGGTGGC 1406 CCACCGCCCGCGCCGCGAC GTCGCGGCGCGGGCGGTGG 1407CACCGCCCGCGCCGCGACC GGTCGCGGCGCGGGCGGTG 1408 ACCGCCCGCGCCGCGACCGCGGTCGCGGCGCGGGCGGT 1409 CCGCCCGCGCCGCGACCGG CCGGTCGCGGCGCGGGCGG 1410CGCCCGCGCCGCGACCGGC GCCGGTCGCGGCGCGGGCG 1411 GCCCGCGCCGCGACCGGCCGGCCGGTCGCGGCGCGGGC 1412 CCCGCGCCGCGACCGGCCG CGGCCGGTCGCGGCGCGGG 1413CCGCGCCGCGACCGGCCGG CCGGCCGGTCGCGGCGCGG 1414 CGCGCCGCGACCGGCCGGTACCGGCCGGTCGCGGCGCG 1415 GCGCCGCGACCGGCCGGTG CACCGGCCGGTCGCGGCGC 1416CGCCGCGACCGGCCGGTGA TCACCGGCCGGTCGCGGCG 1417 GCCGCGACCGGCCGGTGAATTCACCGGCCGGTCGCGGC 1418 CCGCGACCGGCCGGTGAAG CTTCACCGGCCGGTCGCGG 1419CGCGACCGGCCGGTGAAGC GCTTCACCGGCCGGTCGCG 1420 GCGACCGGCCGGTGAAGCCGGCTTCACCGGCCGGTCGC 1421 CGACCGGCCGGTGAAGCCC GGGCTTCACCGGCCGGTCG 1422GACCGGCCGGTGAAGCCCA TGGGCTTCACCGGCCGGTC 1423 ACCGGCCGGTGAAGCCCAGCTGGGCTTCACCGGCCGGT 1424 CCGGCCGGTGAAGCCCAGG CCTGGGCTTCACCGGCCGG 1425CGGCCGGTGAAGCCCAGGG CCCTGGGCTTCACCGGCCG 1426 GGCCGGTGAAGCCCAGGGATCCCTGGGCTTCACCGGCC 1427 GCCGGTGAAGCCCAGGGAC GTCCCTGGGCTTCACCGGC 1428CCGGTGAAGCCCAGGGACC GGTCCCTGGGCTTCACCGG 1429 CGGTGAAGCCCAGGGACCCGGGTCCCTGGGCTTCACCG 1430 GGTGAAGCCCAGGGACCCC GGGGTCCCTGGGCTTCACC 1431GTGAAGCCCAGGGACCCCC GGGGGTCCCTGGGCTTCAC 1432 TGAAGCCCAGGGACCCCCCGGGGGGTCCCTGGGCTTCA 1433 GAAGCCCAGGGACCCCCCT AGGGGGGTCCCTGGGCTTC 1434AAGCCCAGGGACCCCCCTC GAGGGGGGTCCCTGGGCTT 1435 AGCCCAGGGACCCCCCTCTAGAGGGGGGTCCCTGGGCT 1436 GCCCAGGGACCCCCCTCTG CAGAGGGGGGTCCCTGGGC 1437CCCAGGGACCCCCCTCTGG CCAGAGGGGGGTCCCTGGG 1438 CCAGGGACCCCCCTCTGGGCCCAGAGGGGGGTCCCTGG 1439 CAGGGACCCCCCTCTGGGA TCCCAGAGGGGGGTCCCTG 1440AGGGACCCCCCTCTGGGAG CTCCCAGAGGGGGGTCCCT 1441 GGGACCCCCCTCTGGGAGATCTCCCAGAGGGGGGTCCC 1442 GGACCCCCCTCTGGGAGAG CTCTCCCAGAGGGGGGTCC 1443GACCCCCCTCTGGGAGAGC GCTCTCCCAGAGGGGGGTC 1444 ACCCCCCTCTGGGAGAGCCGGCTCTCCCAGAGGGGGGT 1445 CCCCCCTCTGGGAGAGCCC GGGCTCTCCCAGAGGGGGG 1446CCCCCTCTGGGAGAGCCCC GGGGCTCTCCCAGAGGGGG 1447 CCCCTCTGGGAGAGCCCCATGGGGCTCTCCCAGAGGGG 1448 CCCTCTGGGAGAGCCCCAT ATGGGGCTCTCCCAGAGGG 1449CCTCTGGGAGAGCCCCATG CATGGGGCTCTCCCAGAGG 1450 CTCTGGGAGAGCCCCATGATCATGGGGCTCTCCCAGAG 1451 TCTGGGAGAGCCCCATGAG CTCATGGGGCTCTCCCAGA 1452CTGGGAGAGCCCCATGAGG CCTCATGGGGCTCTCCCAG 1453 TGGGAGAGCCCCATGAGGGCCCTCATGGGGCTCTCCCA 1454 GGGAGAGCCCCATGAGGGC GCCCTCATGGGGCTCTCCC 1455GGAGAGCCCCATGAGGGCA TGCCCTCATGGGGCTCTCC 1456 GAGAGCCCCATGAGGGCAGCTGCCCTCATGGGGCTCTC 1457 AGAGCCCCATGAGGGCAGG CCTGCCCTCATGGGGCTCT 1458GAGCCCCATGAGGGCAGGA TCCTGCCCTCATGGGGCTC 1459 AGCCCCATGAGGGCAGGAGCTCCTGCCCTCATGGGGCT 1460 GCCCCATGAGGGCAGGAGA TCTCCTGCCCTCATGGGGC 1461CCCCATGAGGGCAGGAGAG CTCTCCTGCCCTCATGGGG 1462 CCCATGAGGGCAGGAGAGTACTCTCCTGCCCTCATGGG 1463 CCATGAGGGCAGGAGAGTG CACTCTCCTGCCCTCATGG 1464CATGAGGGCAGGAGAGTGA TCACTCTCCTGCCCTCATG 1465 ATGAGGGCAGGAGAGTGATATCACTCTCCTGCCCTCAT 1466 TGAGGGCAGGAGAGTGATG CATCACTCTCCTGCCCTCA 1467GAGGGCAGGAGAGTGATGG CCATCACTCTCCTGCCCTC 1468 AGGGCAGGAGAGTGATGGATCCATCACTCTCCTGCCCT 1469 GGGCAGGAGAGTGATGGAG CTCCATCACTCTCCTGCCC 1470GGCAGGAGAGTGATGGAGA TCTCCATCACTCTCCTGCC 1471 GCAGGAGAGTGATGGAGAGCTCTCCATCACTCTCCTGC 1472 CAGGAGAGTGATGGAGAGT ACTCTCCATCACTCTCCTG 1473AGGAGAGTGATGGAGAGTA TACTCTCCATCACTCTCCT 1474 GGAGAGTGATGGAGAGTACGTACTCTCCATCACTCTCC 1475 GAGAGTGATGGAGAGTACG CGTACTCTCCATCACTCTC 1476AGAGTGATGGAGAGTACGC GCGTACTCTCCATCACTCT 1477 GAGTGATGGAGAGTACGCCGGCGTACTCTCCATCACTC 1478 AGTGATGGAGAGTACGCCC GGGCGTACTCTCCATCACT 1479GTGATGGAGAGTACGCCCA TGGGCGTACTCTCCATCAC 1480 TGATGGAGAGTACGCCCAGCTGGGCGTACTCTCCATCA 1481 GATGGAGAGTACGCCCAGC GCTGGGCGTACTCTCCATC 1482ATGGAGAGTACGCCCAGCT AGCTGGGCGTACTCTCCAT 1483 TGGAGAGTACGCCCAGCTTAAGCTGGGCGTACTCTCCA 1484 GGAGAGTACGCCCAGCTTC GAAGCTGGGCGTACTCTCC 1485GAGAGTACGCCCAGCTTCC GGAAGCTGGGCGTACTCTC 1486 AGAGTACGCCCAGCTTCCTAGGAAGCTGGGCGTACTCT 1487 GAGTACGCCCAGCTTCCTG CAGGAAGCTGGGCGTACTC 1488AGTACGCCCAGCTTCCTGA TCAGGAAGCTGGGCGTACT 1489 GTACGCCCAGCTTCCTGAATTCAGGAAGCTGGGCGTAC 1490 TACGCCCAGCTTCCTGAAG CTTCAGGAAGCTGGGCGTA 1491ACGCCCAGCTTCCTGAAGG CCTTCAGGAAGCTGGGCGT 1492 CGCCCAGCTTCCTGAAGGGCCCTTCAGGAAGCTGGGCG 1493 GCCCAGCTTCCTGAAGGGC GCCCTTCAGGAAGCTGGGC 1494CCCAGCTTCCTGAAGGGCA TGCCCTTCAGGAAGCTGGG 1495 CCAGCTTCCTGAAGGGCACGTGCCCTTCAGGAAGCTGG 1496 CAGCTTCCTGAAGGGCACC GGTGCCCTTCAGGAAGCTG 1497AGCTTCCTGAAGGGCACCC GGGTGCCCTTCAGGAAGCT 1498 GCTTCCTGAAGGGCACCCCGGGGTGCCCTTCAGGAAGC 1499 CTTCCTGAAGGGCACCCCA TGGGGTGCCCTTCAGGAAG 1500TTCCTGAAGGGCACCCCAA TTGGGGTGCCCTTCAGGAA 1501 TCCTGAAGGGCACCCCAACGTTGGGGTGCCCTTCAGGA 1502 CCTGAAGGGCACCCCAACC GGTTGGGGTGCCCTTCAGG 1503CTGAAGGGCACCCCAACCT AGGTTGGGGTGCCCTTCAG 1504 TGAAGGGCACCCCAACCTGCAGGTTGGGGTGCCCTTCA 1505 GAAGGGCACCCCAACCTGG CCAGGTTGGGGTGCCCTTC 1506AAGGGCACCCCAACCTGGG CCCAGGTTGGGGTGCCCTT 1507 AGGGCACCCCAACCTGGGATCCCAGGTTGGGGTGCCCT 1508 GGGCACCCCAACCTGGGAG CTCCCAGGTTGGGGTGCCC 1509GGCACCCCAACCTGGGAGA TCTCCCAGGTTGGGGTGCC 1510 GCACCCCAACCTGGGAGAATTCTCCCAGGTTGGGGTGC 1511 CACCCCAACCTGGGAGAAG CTTCTCCCAGGTTGGGGTG 1512ACCCCAACCTGGGAGAAGA TCTTCTCCCAGGTTGGGGT 1513 CCCCAACCTGGGAGAAGACGTCTTCTCCCAGGTTGGGG 1514 CCCAACCTGGGAGAAGACG CGTCTTCTCCCAGGTTGGG 1515CCAACCTGGGAGAAGACGG CCGTCTTCTCCCAGGTTGG 1516 CAACCTGGGAGAAGACGGCGCCGTCTTCTCCCAGGTTG 1517 AACCTGGGAGAAGACGGCC GGCCGTCTTCTCCCAGGTT 1518ACCTGGGAGAAGACGGCCC GGGCCGTCTTCTCCCAGGT 1519 CCTGGGAGAAGACGGCCCCGGGGCCGTCTTCTCCCAGG 1520 CTGGGAGAAGACGGCCCCA TGGGGCCGTCTTCTCCCAG 1521TGGGAGAAGACGGCCCCAG CTGGGGCCGTCTTCTCCCA 1522 GGGAGAAGACGGCCCCAGATCTGGGGCCGTCTTCTCCC 1523 GGAGAAGACGGCCCCAGAG CTCTGGGGCCGTCTTCTCC 1524GAGAAGACGGGGCCAGAGA TCTCTGGGGCCGTCTTCTC 1525 AGAAGACGGCCCCAGAGAATTCTCTGGGGCCGTCTTCT 1526 GAAGACGGCCCCAGAGAAC GTTCTCTGGGGCCGTCTTC 1527AAGACGGCCCCAGAGAACG CGTTCTCTGGGGCCGTCTT 1528 AGACGGCCCCAGAGAACGGCCGTTCTCTGGGGCCGTCT 1529 GACGGCCCCAGAGAACGGC GCCGTTCTCTGGGGCCGTC 1530ACGGCCCCAGAGAACGGCA TGCCGTTCTCTGGGGCCGT 1531 CGGCCCCAGAGAACGGCATATGCCGTTCTCTGGGGCCG 1532 GGCCCCAGAGAACGGCATC GATGCCGTTCTCTGGGGCC 1533GCCCCAGAGAACGGCATCG CGATGCCGTTCTCTGGGGC 1534 CCCCAGAGAACGGCATCGTACGATGCCGTTCTCTGGGG 1535 CCCAGAGAACGGCATCGTG CACGATGCCGTTCTCTGGG 1536CCAGAGAACGGCATCGTGA TCACGATGCCGTTCTCTGG 1537 CAGAGAACGGCATCGTGAGCTCACGATGCCGTTCTCTG 1538 AGAGAACGGCATCGTGAGA TCTCACGATGCCGTTCTCT 1539GAGAACGGCATCGTGAGAC GTCTCACGATGCCGTTCTC 1540 AGAACGGCATCGTGAGACATGTCTCACGATGCCGTTCT 1541 GAACGGCATCGTGAGACAG CTGTCTCACGATGCCGTTC 1542AACGGCATCGTGAGACAGG CCTGTCTCACGATGCCGTT 1543 ACGGCATCGTGAGACAGGATCCTGTCTCACGATGCCGT 1544 CGGCATCGTGAGACAGGAG CTCCTGTCTCACGATGCCG 1545GGCATCGTGAGACAGGAGC GCTCCTGTCTCACGATGCC 1546 GCATCGTGAGACAGGAGCCGGCTCCTGTCTCACGATGC 1547 CATCGTGAGACAGGAGCCC GGGCTCCTGTCTCACGATG 1548ATCGTGAGACAGGAGCCCG CGGGCTCCTGTCTCACGAT 1549 TCGTGAGACAGGAGCCCGGCCGGGCTCCTGTCTCACGA 1550 CGTGAGACAGGAGCCCGGC GCCGGGCTCCTGTCTCACG 1551GTGAGACAGGAGCCCGGCA TGCCGGGCTCCTGTCTCAC 1552 TGAGACAGGAGCCCGGCAGCTGCCGGGCTCCTGTCTCA 1553 GAGACAGGAGCCCGGCAGC GCTGCCGGGCTCCTGTCTC 1554AGACAGGAGCCCGGCAGCC GGCTGCCGGGCTCCTGTCT 1555 GACAGGAGCCCGGCAGCCCGGGCTGCCGGGCTCCTGTC 1556 ACAGGAGCCCGGCAGCCCG CGGGCTGCCGGGCTCCTGT 1557CAGGAGCCCGGCAGCCCGC GCGGGCTGCCGGGCTCCTG 1558 AGGAGCCCGGCAGCCCGCCGGCGGGCTGCCGGGCTCCT 1559 GGAGCCCGGCAGCCCGCCT AGGCGGGCTGCCGGGCTCC 1560GAGCCCGGCAGCCCGCCTC GAGGCGGGCTGCCGGGCTC 1561 AGCCCGGCAGCCCGCCTCGCGAGGCGGGCTGCCGGGCT 1562 GCCCGGCAGCCCGCCTCGA TCGAGGCGGGCTGCCGGGC 1563CCCGGCAGCCCGCCTCGAG CTCGAGGCGGGCTGCCGGG 1564 CCGGCAGCCCGCCTCGAGATCTCGAGGCGGGCTGCCGG 1565 CGGCAGCCCGCCTCGAGAT ATCTCGAGGCGGGCTGCCG 1566GGCAGCCCGCCTCGAGATG CATCTCGAGGCGGGCTGCC 1567 GCAGCCCGCCTCGAGATGGCCATCTCGAGGCGGGCTGC 1568 CAGCCCGCCTCGAGATGGA TCCATCTCGAGGCGGGCTG 1569AGCCCGCCTCGAGATGGAC GTCCATCTCGAGGCGGGCT 1570 GCCCGCCTCGAGATGGACTAGTCCATCTCGAGGCGGGC 1571 CCCGCCTCGAGATGGACTG CAGTCCATCTCGAGGCGGG 1572CCGCCTCGAGATGGACTGC GCAGTCCATCTCGAGGCGG 1573 CGCCTCGAGATGGACTGCATGCAGTCCATCTCGAGGCG 1574 GCCTCGAGATGGACTGCAC GTGCAGTCCATCTCGAGGC 1575CCTCGAGATGGACTGCACC GGTGCAGTCCATCTCGAGG 1576 CTCGAGATGGACTGCACCATGGTGCAGTCCATCTCGAG 1577 TCGAGATGGACTGCACCAT ATGGTGCAGTCCATCTCGA 1578CGAGATGGACTGCACCATG CATGGTGCAGTCCATCTCG 1579 GAGATGGACTGCACCATGGCCATGGTGCAGTCCATCTC 1580 AGATGGACTGCACCATGGG CCCATGGTGCAGTCCATCT 1581GATGGACTGCACCATGGGC GCCCATGGTGCAGTCCATC 1582 ATGGACTGCACCATGGGCCGGCCCATGGTGCAGTCCAT 1583 TGGACTGCACCATGGGCCG CGGCCCATGGTGCAGTCCA 1584GGACTGCACCATGGGCCGC GCGGCCCATGGTGCAGTCC 1585 GACTGCACCATGGGCCGCTAGCGGCCCATGGTGCAGTC 1586 ACTGCACCATGGGCCGCTG CAGCGGCCCATGGTGCAGT 1587CTGCACCATGGGCCGCTGT ACAGCGGCCCATGGTGCAG 1588 TGCACCATGGGCCGCTGTGCACAGCGGCCCATGGTGCA 1589 GCACCATGGGCCGCTGTGC GCACAGCGGCCCATGGTGC 1590CACCATGGGCCGCTGTGCC GGCACAGCGGCCCATGGTG 1591 ACCATGGGCCGCTGTGCCTAGGCACAGCGGCCCATGGT 1592 CCATGGGCCGCTGTGCCTG CAGGCACAGCGGCCCATGG 1593CATGGGCCGCTGTGCCTGG CCAGGCACAGCGGCCCATG 1594 ATGGGCCGCTGTGCCTGGGCCCAGGCACAGCGGCCCAT 1595 TGGGCCGCTGTGCCTGGGA TCCCAGGCACAGCGGCCCA 1596GGGCCGCTGTGCCTGGGAG CTCCCAGGCACAGCGGCCC 1597 GGCCGCTGTGCCTGGGAGATCTCCCAGGCACAGCGGCC 1598 GCCGCTGTGCCTGGGAGAG CTCTCCCAGGCACAGCGGC 1599CCGCTGTGCCTGGGAGAGC GCTCTCCCAGGCACAGCGG 1600 CGCTGTGCCTGGGAGAGCCGGCTCTCCCAGGCACAGCG 1601 GCTGTGCCTGGGAGAGCCT AGGCTCTCCCAGGCACAGC 1602CTGTGCCTGGGAGAGCCTG CAGGCTCTCCCAGGCACAG 1603 TGTGCCTGGGAGAGCCTGCGCAGGCTCTCCCAGGCACA 1604 GTGCCTGGGAGAGCCTGCT AGCAGGCTCTCCCAGGCAC 1605TGCCTGGGAGAGCCTGCTC GAGCAGGCTCTCCCAGGCA 1606 GCCTGGGAGAGCCTGCTCCGGAGCAGGCTCTCCCAGGC 1607 CCTGGGAGAGCCTGCTCCC GGGAGCAGGCTCTCCCAGG 1608CTGGGAGAGCCTGCTCCCT AGGGAGCAGGCTCTCCCAG 1609 TGGGAGAGCCTGCTCCCTTAAGGGAGCAGGCTCTCCCA 1610 GGGAGAGCCTGCTCCCTTT AAAGGGAGCAGGCTCTCCC 1611GGAGAGCCTGCTCCCTTTT AAAAGGGAGCAGGCTCTCC 1612 GAGAGCCTGCTCCCTTTTGCAAAAGGGAGCAGGCTCTC 1613 AGAGCCTGCTCCCTTTTGG CCAAAAGGGAGCAGGCTCT 1614GAGCCTGCTCCCTTTTGGA TCCAAAAGGGAGCAGGCTC 1615 AGCCTGCTCCCTTTTGGAGCTCCAAAAGGGAGCAGGCT 1616 GCCTGCTCCCTTTTGGAGG CCTCCAAAAGGGAGCAGGC 1617CCTGCTCCCTTTTGGAGGG CCCTCCAAAAGGGAGCAGG 1618 CTGCTCCCTTTTGGAGGGGCCCCTCCAAAAGGGAGCAG 1619 TGCTCCCTTTTGGAGGGGC GCCCCTCCAAAAGGGAGCA 1620GCTCCCTTTTGGAGGGGCG CGCCCCTCCAAAAGGGAGC 1621 CTCCCTTTTGGAGGGGCGTACGCCCCTCCAAAAGGGAG 1622 TCCCTTTTGGAGGGGCGTC GACGCCCCTCCAAAAGGGA 1623CCCTTTTGGAGGGGCGTCC GGACGCCCCTCCAAAAGGG 1624 CCTTTTGGAGGGGCGTCCTAGGACGCCCCTCCAAAAGG 1625 CTTTTGGAGGGGCGTCCTG CAGGACGCCCCTCCAAAAG 1626TTTTGGAGGGGCGTCCTGA TCAGGACGCCCCTCCAAAA 1627 TTTGGAGGGGCGTCCTGAGCTCAGGACGCCCCTCCAAA 1628 TTGGAGGGGCGTCCTGAGC GCTCAGGACGCCCCTCCAA 1629TGGAGGGGCGTCCTGAGCA TGCTCAGGACGCCCCTCCA 1630 GGAGGGGCGTCCTGAGCACGTGCTCAGGACGCCCCTCC 1631 GAGGGGCGTCCTGAGCACC GGTGCTCAGGACGCCCCTC 1632AGGGGCGTCCTGAGCACCC GGGTGCTCAGGACGCCCCT 1633 GGGGCGTCCTGAGCACCCCGGGGTGCTCAGGACGCCCC 1634 GGGCGTCCTGAGCACCCCA TGGGGTGCTCAGGACGCCC 1635GGCGTCCTGAGCACCCCAG CTGGGGTGCTCAGGACGCC 1636 GCGTCCTGAGCACCCCAGATCTGGGGTGCTCAGGACGC 1637 CGTCCTGAGCACCCCAGAC GTCTGGGGTGCTCAGGACG 1638GTCCTGAGCACCCCAGACT AGTCTGGGGTGCTCAGGAC 1639 TCCTGAGCACCCCAGACTCGAGTCTGGGGTGCTCAGGA 1640 CCTGAGCACCCCAGACTCC GGAGTCTGGGGTGCTCAGG 1641CTGAGCACCCCAGACTCCT AGGAGTCTGGGGTGCTCAG 1642 TGAGCACCCCAGACTCCTGCAGGAGTCTGGGGTGCTCA 1643 GAGCACCCCAGACTCCTGG CCAGGAGTCTGGGGTGCTC 1644AGCACCCCAGACTCCTGGC GCCAGGAGTCTGGGGTGCT 1645 GCACCCCAGACTCCTGGCTAGCCAGGAGTCTGGGGTGC 1646 CACCCCAGACTCCTGGCTT AAGCCAGGAGTCTGGGGTG 1647ACCCCAGACTCCTGGCTTC GAAGCCAGGAGTCTGGGGT 1648 CCCCAGACTCCTGGCTTCCGGAAGCCAGGAGTCTGGGG 1649 CCCAGACTCCTGGCTTCCC GGGAAGCCAGGAGTCTGGG 1650CCAGACTCCTGGCTTCCCC GGGGAAGCCAGGAGTCTGG 1651 CAGACTCCTGGCTTCCCCCGGGGGAAGCCAGGAGTCTG 1652 AGACTCCTGGCTTCCCCCT AGGGGGAAGCCAGGAGTCT 1653GACTCCTGGCTTCCCCCTG CAGGGGGAAGCCAGGAGTC 1654 ACTCCTGGCTTCCCCCTGGCCAGGGGGAAGCCAGGAGT 1655 CTCCTGGCTTCCCCCTGGC GCCAGGGGGAAGCCAGGAG 1656TCCTGGCTTCCCCCTGGCT AGCCAGGGGGAAGCCAGGA 1657 CCTGGCTTCCCCCTGGCTTAAGCCAGGGGGAAGCCAGG 1658 CTGGCTTCCCCCTGGCTTC GAAGCCAGGGGGAAGCCAG 1659TGGCTTCCCCCTGGCTTCC GGAAGCCAGGGGGAAGCCA 1660 GGCTTCCCCCTGGCTTCCCGGGAAGCCAGGGGGAAGCC 1661 GCTTCCCCCTGGCTTCCCC GGGGAAGCCAGGGGGAAGC 1662CTTCCCCCTGGCTTCCCCC GGGGGAAGCCAGGGGGAAG 1663 TTCCCCCTGGCTTCCCCCATGGGGGAAGCCAGGGGGAA 1664 TCCCCCTGGCTTCCCCCAG CTGGGGGAAGCCAGGGGGA 1665CCCCCTGGCTTCCCCCAGG CCTGGGGGAAGCCAGGGGG 1666 CCCCTGGCTTCCCCCAGGGCCCTGGGGGAAGCCAGGGG 1667 CCCTGGCTTCCCCCAGGGC GCCCTGGGGGAAGCCAGGG 1668CCTGGCTTCCCCCAGGGCC GGCCCTGGGGGAAGCCAGG 1669 CTGGCTTCCCCCAGGGCCCGGGCCCTGGGGGAAGCCAG 1670 TGGCTTCCCCCAGGGCCCC GGGGCCCTGGGGGAAGCCA 1671GGCTTCCCCCAGGGCCCCA TGGGGCCCTGGGGGAAGCC 1672 GCTTCCCCCAGGGCCCCAATTGGGGCCCTGGGGGAAGC 1673 CTTCCCCCAGGGCCCCAAG CTTGGGGCCCTGGGGGAAG 1674TTCCCCCAGGGCCCCAAGG CCTTGGGGCCCTGGGGGAA 1675 TCCCCCAGGGCCCCAAGGATCCTTGGGGCCCTGGGGGA 1676 CCCCCAGGGCCCCAAGGAC GTCCTTGGGGCCCTGGGGG 1677CCCCAGGGCCCCAAGGACA TGTCCTTGGGGCCCTGGGG 1678 CCCAGGGCCCCAAGGACATATGTCCTTGGGGCCCTGGG 1679 CCAGGGCCCCAAGGACATG CATGTCCTTGGGGCCCTGG 1680CAGGGCCCCAAGGACATGC GCATGTCCTTGGGGCCCTG 1681 AGGGCCCCAAGGACATGCTAGCATGTCCTTGGGGCCCT 1682 GGGCCCCAAGGACATGCTC GAGCATGTCCTTGGGGCCC 1683GGCCCCAAGGACATGCTCC GGAGCATGTCCTTGGGGCC 1684 GCCCCAAGGACATGCTCCCGGGAGCATGTCCTTGGGGC 1685 CCCCAAGGACATGCTCCCA TGGGAGCATGTCCTTGGGG 1686CCCAAGGACATGCTCCCAC GTGGGAGCATGTCCTTGGG 1687 CCAAGGACATGCTCCCACTAGTGGGAGCATGTCCTTGG 1688 CAAGGACATGCTCCCACTT AAGTGGGAGCATGTCCTTG 1689AAGGACATGCTCCCACTTG CAAGTGGGAGCATGTCCTT 1690 AGGACATGCTCCCACTTGTACAAGTGGGAGCATGTCCT 1691 GGACATGCTCCCACTTGTG CACAAGTGGGAGCATGTCC 1692GACATGCTCCCACTTGTGG CCACAAGTGGGAGCATGTC 1693 ACATGCTCCCACTTGTGGATCCACAAGTGGGAGCATGT 1694 CATGCTCCCACTTGTGGAG CTCCACAAGTGGGAGCATG 1695ATGCTCCCACTTGTGGAGG CCTCCACAAGTGGGAGCAT 1696 TGCTCCCACTTGTGGAGGGCCCTCCACAAGTGGGAGCA 1697 GCTCCCACTTGTGGAGGGC GCCCTCCACAAGTGGGAGC 1698CTCCCACTTGTGGAGGGCG CGCCCTCCACAAGTGGGAG 1699 TCCCACTTGTGGAGGGCGATCGCCCTCCACAAGTGGGA 1700 CCCACTTGTGGAGGGCGAG CTCGCCCTCCACAAGTGGG 1701CCACTTGTGGAGGGCGAGG CCTCGCCCTCCACAAGTGG 1702 CACTTGTGGAGGGCGAGGGCCCTCGCCCTCCACAAGTG 1703 ACTTGTGGAGGGCGAGGGC GCCCTCGCCCTCCACAAGT 1704CTTGTGGAGGGCGAGGGCC GGCCCTCGCCCTCCACAAG 1705 TTGTGGAGGGCGAGGGCCCGGGCCCTCGCCCTCCACAA 1706 TGTGGAGGGCGAGGGCCCC GGGGCCCTCGCCCTCCACA 1707GTGGAGGGCGAGGGCCCCC GGGGGCCCTCGCCCTCCAC 1708 TGGAGGGCGAGGGCCCCCATGGGGGCCCTCGCCCTCCA 1709 GGAGGGCGAGGGCCCCCAG CTGGGGGCCCTCGCCCTCC 1710GAGGGCGAGGGCCCCCAGA TCTGGGGGCCCTCGCCCTC 1711 AGGGCGAGGGCCCCCAGAATTCTGGGGGCCCTCGCCCT 1712 GGGCGAGGGCCCCCAGAAT ATTCTGGGGGCCCTCGCCC 1713GGCGAGGGCCCCCAGAATG CATTCTGGGGGCCCTCGCC 1714 GCGAGGGCCCCCAGAATGGCCATTCTGGGGGCCCTCGC 1715 CGAGGGCCCCCAGAATGGG CCCATTCTGGGGGCCCTCG 1716GAGGGCCCCCAGAATGGGG CCCCATTCTGGGGGCCCTC 1717 AGGGCCCCCAGAATGGGGATCCCCATTCTGGGGGCCCT 1718 GGGCCCCCAGAATGGGGAG CTCCCCATTCTGGGGGCCC 1719GGCCCCCAGAATGGGGAGA TCTCCCCATTCTGGGGGCC 1720 GCCCCCAGAATGGGGAGAGCTCTCCCCATTCTGGGGGC 1721 CCCCCAGAATGGGGAGAGG CCTCTCCCCATTCTGGGGG 1722CCCCAGAATGGGGAGAGGA TCCTCTCCCCATTCTGGGG 1723 CCCAGAATGGGGAGAGGAATTCCTCTCCCCATTCTGGG 1724 CCAGAATGGGGAGAGGAAG CTTCCTCTCCCCATTCTGG 1725CAGAATGGGGAGAGGAAGG CCTTCCTCTCCCCATTCTG 1726 AGAATGGGGAGAGGAAGGTACCTTCCTCTCCCCATTCT 1727 GAATGGGGAGAGGAAGGTC GACCTTCCTCTCCCCATTC 1728AATGGGGAGAGGAAGGTCA TGACCTTCCTCTCCCCATT 1729 ATGGGGAGAGGAAGGTCAATTGACCTTCCTCTCCCCAT 1730 TGGGGAGAGGAAGGTCAAC GTTGACCTTCCTCTCCCCA 1731GGGGAGAGGAAGGTCAACT AGTTGACCTTCCTCTCCCC 1732 GGGAGAGGAAGGTCAACTGCAGTTGACCTTCCTCTCCC 1733 GGAGAGGAAGGTCAACTGG CCAGTTGACCTTCCTCTCC 1734GAGAGGAAGGTCAACTGGC GCCAGTTGACCTTCCTCTC 1735 AGAGGAAGGTCAACTGGCTAGCCAGTTGACCTTCCTCT 1736 GAGGAAGGTCAACTGGCTG CAGCCAGTTGACCTTCCTC 1737AGGAAGGTCAACTGGCTGG CCAGCCAGTTGACCTTCCT 1738 GGAAGGTCAACTGGCTGGGCCCAGCCAGTTGACCTTCC 1739 GAAGGTCAACTGGCTGGGC GCCCAGCCAGTTGACCTTC 1740AAGGTCAACTGGCTGGGCA TGCCCAGCCAGTTGACCTT 1741 AGGTCAACTGGCTGGGCAGCTGCCCAGCCAGTTGACCT 1742 GGTCAACTGGCTGGGCAGC GCTGCCCAGCCAGTTGACC 1743GTCAACTGGCTGGGCAGCA TGCTGCCCAGCCAGTTGAC 1744 TCAACTGGCTGGGCAGCAATTGCTGCCCAGCCAGTTGA 1745 CAACTGGCTGGGCAGCAAA TTTGCTGCCCAGCCAGTTG 1746AACTGGCTGGGCAGCAAAG CTTTGCTGCCCAGCCAGTT 1747 ACTGGCTGGGCAGCAAAGATCTTTGCTGCCCAGCCAGT 1748 CTGGCTGGGCAGCAAAGAG CTCTTTGCTGCCCAGCCAG 1749TGGCTGGGCAGCAAAGAGG CCTCTTTGCTGCCCAGCCA 1750 GGCTGGGCAGCAAAGAGGGCCCTCTTTGCTGCCCAGCC 1751 GCTGGGCAGCAAAGAGGGA TCCCTCTTTGCTGCCCAGC 1752CTGGGCAGCAAAGAGGGAC GTCCCTCTTTGCTGCCCAG 1753 TGGGCAGCAAAGAGGGACTAGTCCCTCTTTGCTGCCCA 1754 GGGCAGCAAAGAGGGACTG CAGTCCCTCTTTGCTGCCC 1755GGCAGCAAAGAGGGACTGC GCAGTCCCTCTTTGCTGCC 1756 GCAGCAAAGAGGGACTGCGCGCAGTCCCTCTTTGCTGC 1757 CAGCAAAGAGGGACTGCGC GCGCAGTCCCTCTTTGCTG 1758AGCAAAGAGGGACTGCGCT AGCGCAGTCCCTCTTTGCT 1759 GCAAAGAGGGACTGCGCTGCAGCGCAGTCCCTCTTTGC 1760 CAAAGAGGGACTGCGCTGG CCAGCGCAGTCCCTCTTTG 1761AAAGAGGGACTGCGCTGGA TCCAGCGCAGTCCCTCTTT 1762 AAGAGGGACTGCGCTGGAATTCCAGCGCAGTCCCTCTT 1763 AGAGGGACTGCGCTGGAAG CTTCCAGCGCAGTCCCTCT 1764GAGGGACTGCGCTGGAAGG CCTTCCAGCGCAGTCCCTC 1765 AGGGACTGCGCTGGAAGGATCCTTCCAGCGCAGTCCCT 1766 GGGACTGCGCTGGAAGGAG CTCCTTCCAGCGCAGTCCC 1767GGACTGCGCTGGAAGGAGG CCTCCTTCCAGCGCAGTCC 1768 GACTGCGCTGGAAGGAGGCGCCTCCTTCCAGCGCAGTC 1769 ACTGCGCTGGAAGGAGGCC GGCCTCCTTCCAGCGCAGT 1770CTGCGCTGGAAGGAGGCCA TGGCCTCCTTCCAGCGCAG 1771 TGCGCTGGAAGGAGGCCATATGGCCTCCTTCCAGCGCA 1772 GCGCTGGAAGGAGGCCATG CATGGCCTCCTTCCAGCGC 1773CGCTGGAAGGAGGCCATGC GCATGGCCTCCTTCCAGCG 1774 GCTGGAAGGAGGCCATGCTAGCATGGCCTCCTTCCAGC 1775 CTGGAAGGAGGCCATGCTT AAGCATGGCCTCCTTCCAG 1776TGGAAGGAGGCCATGCTTA TAAGCATGGCCTCCTTCCA 1777 GGAAGGAGGCCATGCTTACGTAAGCATGGCCTCCTTCC 1778 GAAGGAGGCCATGCTTACC GGTAAGCATGGCCTCCTTC 1779AAGGAGGCCATGCTTACCC GGGTAAGCATGGCCTCCTT 1780 AGGAGGCCATGCTTACCCATGGGTAAGCATGGCCTCCT 1781 GGAGGCCATGCTTACCCAT ATGGGTAAGCATGGCCTCC 1782GAGGCCATGCTTACCCATC GATGGGTAAGCATGGCCTC 1783 AGGCCATGCTTACCCATCCGGATGGGTAAGCATGGCCT 1784 GGCCATGCTTACCCATCCG CGGATGGGTAAGCATGGCC 1785GCCATGCTTACCCATCCGC GCGGATGGGTAAGCATGGC 1786 CCATGCTTACCCATCCGCTAGCGGATGGGTAAGCATGG 1787 CATGCTTACCCATCCGCTG CAGCGGATGGGTAAGCATG 1788ATGCTTACCCATCCGCTGG CCAGCGGATGGGTAAGCAT 1789 TGCTTACCCATCCGCTGGCGCCAGCGGATGGGTAAGCA 1790 GCTTACCCATCCGCTGGCA TGCCAGCGGATGGGTAAGC 1791CTTACCCATCCGCTGGCAT ATGCCAGCGGATGGGTAAG 1792 TTACCCATCCGCTGGCATTAATGCCAGCGGATGGGTAA 1793 TACCCATCCGCTGGCATTC GAATGCCAGCGGATGGGTA 1794ACCCATCCGCTGGCATTCT AGAATGCCAGCGGATGGGT 1795 CCCATCCGCTGGCATTCTGCAGAATGCCAGCGGATGGG 1796 CCATCCGCTGGCATTCTGC GCAGAATGCCAGCGGATGG 1797CATCCGCTGGCATTCTGCG CGCAGAATGCCAGCGGATG 1798 ATCCGCTGGCATTCTGCGGCCGCAGAATGCCAGCGGAT 1799 TCCGCTGGCATTCTGCGGG CCCGCAGAATGCCAGCGGA 1800CCGCTGGCATTCTGCGGGC GCCCGCAGAATGCCAGCGG 1801 CGCTGGCATTCTGCGGGCCGGCCCGCAGAATGCCAGCG 1802 GCTGGCATTCTGCGGGCCA TGGCCCGCAGAATGCCAGC 1803CTGGCATTCTGCGGGCCAG CTGGCCCGCAGAATGCCAG 1804 TGGCATTCTGCGGGCCAGCGCTGGCCCGCAGAATGCCA 1805 GGCATTCTGCGGGCCAGCG CGCTGGCCCGCAGAATGCC 1806GCATTCTGCGGGCCAGCGT ACGCTGGCCCGCAGAATGC 1807 CATTCTGCGGGCCAGCGTGCACGCTGGCCCGCAGAATG 1808 ATTCTGCGGGCCAGCGTGC GCACGCTGGCCCGCAGAAT 1809TTCTGCGGGCCAGCGTGCC GGCACGCTGGCCCGCAGAA 1810 TCTGCGGGCCAGCGTGCCCGGGCACGCTGGCCCGCAGA 1811 CTGCGGGCCAGCGTGCCCA TGGGCACGCTGGCCCGCAG 1812TGCGGGCCAGCGTGCCCAC GTGGGCACGCTGGCCCGCA 1813 GCGGGCCAGCGTGCCCACCGGTGGGCACGCTGGCCCGC 1814 CGGGCCAGCGTGCCCACCT AGGTGGGCACGCTGGCCCG 1815GGGCCAGCGTGCCCACCTC GAGGTGGGCACGCTGGCCC 1816 GGCCAGCGTGCCCACCTCGCGAGGTGGGCACGCTGGCC 1817 GCCAGCGTGCCCACCTCGC GCGAGGTGGGCACGCTGGC 1818CCAGCGTGCCCACCTCGCT AGCGAGGTGGGCACGCTGG 1819 CAGCGTGCCCACCTCGCTGCAGCGAGGTGGGCACGCTG 1820 AGCGTGCCCACCTCGCTGT ACAGCGAGGTGGGCACGCT 1821GCGTGCCCACCTCGCTGTG CACAGCGAGGTGGGCACGC 1822 CGTGCCCACCTCGCTGTGGCCACAGCGAGGTGGGCACG 1823 GTGCCCACCTCGCTGTGGC GCCACAGCGAGGTGGGCAC 1824TGCCCACCTCGCTGTGGCC GGCCACAGCGAGGTGGGCA 1825 GCCCACCTCGCTGTGGCCCGGGCCACAGCGAGGTGGGC 1826 CCCACCTCGCTGTGGCCCC GGGGCCACAGCGAGGTGGG 1827CCACCTCGCTGTGGCCCCC GGGGGCCACAGCGAGGTGG 1828 CACCTCGCTGTGGCCCCCTAGGGGGCCACAGCGAGGTG 1829 ACCTCGCTGTGGCCCCCTG CAGGGGGCCACAGCGAGGT 1830CCTCGCTGTGGCCCCCTGA TCAGGGGGCCACAGCGAGG 1831 CTCGCTGTGGCCCCCTGATATCAGGGGGCCACAGCGAG 1832 TCGCTGTGGCCCCCTGATG CATCAGGGGGCCACAGCGA 1833CGCTGTGGCCCCCTGATGC GCATCAGGGGGCCACAGCG 1834 GCTGTGGCCCCCTGATGCCGGCATCAGGGGGCCACAGC 1835 CTGTGGCCCCCTGATGCCT AGGCATCAGGGGGCCACAG 1836TGTGGCCCCCTGATGCCTG CAGGCATCAGGGGGCCACA 1837 GTGGCCCCCTGATGCCTGATCAGGCATCAGGGGGCCAC 1838 TGGCCCCCTGATGCCTGAG CTCAGGCATCAGGGGGCCA 1839GGCCCCCTGATGCCTGAGC GCTCAGGCATCAGGGGGCC 1840 GCCCCCTGATGCCTGAGCATGCTCAGGCATCAGGGGGC 1841 CCCCCTGATGCCTGAGCAT ATGCTCAGGCATCAGGGGG 1842CCCCTGATGCCTGAGCATA TATGCTCAGGCATCAGGGG 1843 CCCTGATGCCTGAGCATAGCTATGCTCAGGCATCAGGG 1844 CCTGATGCCTGAGCATAGT ACTATGCTCAGGCATCAGG 1845CTGATGCCTGAGCATAGTG CACTATGCTCAGGCATCAG 1846 TGATGCCTGAGCATAGTGGCCACTATGCTCAGGCATCA 1847 GATGCCTGAGCATAGTGGT ACCACTATGCTCAGGCATC 1848ATGCCTGAGCATAGTGGTG CACCACTATGCTCAGGCAT 1849 TGCCTGAGCATAGTGGTGGCCACCACTATGCTCAGGCA 1850 GCCTGAGCATAGTGGTGGC GCCACCACTATGCTCAGGC 1851CCTGAGCATAGTGGTGGCC GGCCACCACTATGCTCAGG 1852 CTGAGCATAGTGGTGGCCATGGCCACCACTATGCTCAG 1853 TGAGCATAGTGGTGGCCAT ATGGCCACCACTATGCTCA 1854GAGCATAGTGGTGGCCATC GATGGCCACCACTATGCTC 1855 AGCATAGTGGTGGCCATCTAGATGGCCACCACTATGCT 1856 GCATAGTGGTGGCCATCTC GAGATGGCCACCACTATGC 1857CATAGTGGTGGCCATCTCA TGAGATGGCCACCACTATG 1858 ATAGTGGTGGCCATCTCAATTGAGATGGCCACCACTAT 1859 TAGTGGTGGCCATCTCAAG CTTGAGATGGCCACCACTA 1860AGTGGTGGCCATCTCAAGA TCTTGAGATGGCCACCACT 1861 GTGGTGGCCATCTCAAGAGCTCTTGAGATGGCCACCAC 1862 TGGTGGCCATCTCAAGAGT ACTCTTGAGATGGCCACCA 1863GGTGGCCATCTCAAGAGTG CACTCTTGAGATGGCCACC 1864 GTGGCCATCTCAAGAGTGATCACTCTTGAGATGGCCAC 1865 TGGCCATCTCAAGAGTGAC GTCACTCTTGAGATGGCCA 1866GGCCATCTCAAGAGTGACC GGTCACTCTTGAGATGGCC 1867 GCCATCTCAAGAGTGACCCGGGTCACTCTTGAGATGGC 1868 CCATCTCAAGAGTGACCCT AGGGTCACTCTTGAGATGG 1869CATCTCAAGAGTGACCCTG CAGGGTCACTCTTGAGATG 1870 ATCTCAAGAGTGACCCTGTACAGGGTCACTCTTGAGAT 1871 TCTCAAGAGTGACCCTGTG CACAGGGTCACTCTTGAGA 1872CTCAAGAGTGACCCTGTGG CCACAGGGTCACTCTTGAG 1873 TCAAGAGTGACCCTGTGGCGCCACAGGGTCACTCTTGA 1874 CAAGAGTGACCCTGTGGCC GGCCACAGGGTCACTCTTG 1875AAGAGTGACCCTGTGGCCT AGGCCACAGGGTCACTCTT 1876 AGAGTGACCCTGTGGCCTTAAGGCCACAGGGTCACTCT 1877 GAGTGACCCTGTGGCCTTC GAAGGCCACAGGGTCACTC 1878AGTGACCCTGTGGCCTTCC GGAAGGCCACAGGGTCACT 1879 GTGACCCTGTGGCCTTCCGCGGAAGGCCACAGGGTCAC 1880 TGACCCTGTGGCCTTCCGG CCGGAAGGCCACAGGGTCA 1881GACCCTGTGGCCTTCCGGC GCCGGAAGGCCACAGGGTC 1882 ACCCTGTGGCCTTCCGGCCGGCCGGAAGGCCACAGGGT 1883 CCCTGTGGCCTTCCGGCCC GGGCCGGAAGGCCACAGGG 1884CCTGTGGCCTTCCGGCCCT AGGGCCGGAAGGCCACAGG 1885 CTGTGGCCTTCCGGCCCTGCAGGGCCGGAAGGCCACAG 1886 TGTGGCCTTCCGGCCCTGG CCAGGGCCGGAAGGCCACA 1887GTGGCCTTCCGGCCCTGGC GCCAGGGCCGGAAGGCCAC 1888 TGGCCTTCCGGCCCTGGCATGCCAGGGCCGGAAGGCCA 1889 GGCCTTCCGGCCCTGGCAC GTGCCAGGGCCGGAAGGCC 1890GCCTTCCGGCCCTGGCACT AGTGCCAGGGCCGGAAGGC 1891 CCTTCCGGCCCTGGCACTGCAGTGCCAGGGCCGGAAGG 1892 CTTCCGGCCCTGGCACTGC GCAGTGCCAGGGCCGGAAG 1893TTCCGGCCCTGGCACTGCC GGCAGTGCCAGGGCCGGAA 1894 TCCGGCCCTGGCACTGCCCGGGCAGTGCCAGGGCCGGA 1895 CCGGCCCTGGCACTGCCCT AGGGCAGTGCCAGGGCCGG 1896CGGCCCTGGCACTGCCCTT AAGGGCAGTGCCAGGGCCG 1897 GGCCCTGGCACTGCCCTTTAAAGGGCAGTGCCAGGGCC 1898 GCCCTGGCACTGCCCTTTC GAAAGGGCAGTGCCAGGGC 1899CCCTGGCACTGCCCTTTCC GGAAAGGGCAGTGCCAGGG 1900 CCTGGCACTGCCCTTTCCTAGGAAAGGGCAGTGCCAGG 1901 CTGGCACTGCCCTTTCCTT AAGGAAAGGGCAGTGCCAG 1902TGGCACTGCCCTTTCCTTC GAAGGAAAGGGCAGTGCCA 1903 GGCACTGCCCTTTCCTTCTAGAAGGAAAGGGCAGTGCC 1904 GCACTGCCCTTTCCTTCTG CAGAAGGAAAGGGCAGTGC 1905CACTGCCCTTTCCTTCTGG CCAGAAGGAAAGGGCAGTG 1906 ACTGCCCTTTCCTTCTGGATCCAGAAGGAAAGGGCAGT 1907 CTGCCCTTTCCTTCTGGAG CTCCAGAAGGAAAGGGCAG 1908TGCCCTTTCCTTCTGGAGA TCTCCAGAAGGAAAGGGCA 1909 GCCCTTTCCTTCTGGAGACGTCTCCAGAAGGAAAGGGC 1910 CCCTTTCCTTCTGGAGACC GGTCTCCAGAAGGAAAGGG 1911CCTTTCCTTCTGGAGACCA TGGTCTCCAGAAGGAAAGG 1912 CTTTCCTTCTGGAGACCAATTGGTCTCCAGAAGGAAAG 1913 TTTCCTTCTGGAGACCAAG CTTGGTCTCCAGAAGGAAA 1914TTCCTTCTGGAGACCAAGA TCTTGGTCTCCAGAAGGAA 1915 TCCTTCTGGAGACCAAGATATCTTGGTCTCCAGAAGGA 1916 CCTTCTGGAGACCAAGATC GATCTTGGTCTCCAGAAGG 1917CTTCTGGAGACCAAGATCC GGATCTTGGTCTCCAGAAG 1918 TTCTGGAGACCAAGATCCTAGGATCTTGGTCTCCAGAA 1919 TCTGGAGACCAAGATCCTG CAGGATCTTGGTCTCCAGA 1920CTGGAGACCAAGATCCTGG CCAGGATCTTGGTCTCCAG 1921 TGGAGACCAAGATCCTGGATCCAGGATCTTGGTCTCCA 1922 GGAGACCAAGATCCTGGAG CTCCAGGATCTTGGTCTCC 1923GAGACCAAGATCCTGGAGC GCTCCAGGATCTTGGTCTC 1924 AGACCAAGATCCTGGAGCGCGCTCCAGGATCTTGGTCT 1925 GACCAAGATCCTGGAGCGA TCGCTCCAGGATCTTGGTC 1926ACCAAGATCCTGGAGCGAG CTCGCTCCAGGATCTTGGT 1927 CCAAGATCCTGGAGCGAGCGCTCGCTCCAGGATCTTGG 1928 CAAGATCCTGGAGCGAGCT AGCTCGCTCCAGGATCTTG 1929AAGATCCTGGAGCGAGCTC GAGCTCGCTCCAGGATCTT 1930 AGATCCTGGAGCGAGCTCCGGAGCTCGCTCCAGGATCT 1931 GATCCTGGAGCGAGCTCCC GGGAGCTCGCTCCAGGATC 1932ATCCTGGAGCGAGCTCCCT AGGGAGCTCGCTCCAGGAT 1933 TCCTGGAGCGAGCTCCCTTAAGGGAGCTCGCTCCAGGA 1934 CCTGGAGCGAGCTCCCTTC GAAGGGAGCTCGCTCCAGG 1935CTGGAGCGAGCTCCCTTCT AGAAGGGAGCTCGCTCCAG 1936 TGGAGCGAGCTCCCTTCTGCAGAAGGGAGCTCGCTCCA 1937 GGAGCGAGCTCCCTTCTGG CCAGAAGGGAGCTCGCTCC 1938GAGCGAGCTCCCTTCTGGG CCCAGAAGGGAGCTCGCTC 1939 AGCGAGCTCCCTTCTGGGTACCCAGAAGGGAGCTCGCT 1940 GCGAGCTCCCTTCTGGGTG CACCCAGAAGGGAGCTCGC 1941CGAGCTCCCTTCTGGGTGC GCACCCAGAAGGGAGCTCG 1942 GAGCTCCCTTCTGGGTGCCGGCACCCAGAAGGGAGCTC 1943 AGCTCCCTTCTGGGTGCCC GGGCACCCAGAAGGGAGCT 1944GCTCCCTTCTGGGTGCCCA TGGGCACCCAGAAGGGAGC 1945 CTCCCTTCTGGGTGCCCACGTGGGCACCCAGAAGGGAG 1946 TCCCTTCTGGGTGCCCACC GGTGGGCACCCAGAAGGGA 1947CCCTTCTGGGTGCCCACCT AGGTGGGCACCCAGAAGGG 1948 CCTTCTGGGTGCCCACCTGCAGGTGGGCACCCAGAAGG 1949 CTTCTGGGTGCCCACCTGC GCAGGTGGGCACCCAGAAG 1950TTCTGGGTGCCCACCTGCT AGCAGGTGGGCACCCAGAA 1951 TCTGGGTGCCCACCTGCTTAAGCAGGTGGGCACCCAGA 1952 CTGGGTGCCCACCTGCTTG CAAGCAGGTGGGCACCCAG 1953TGGGTGCCCACCTGCTTGC GCAAGCAGGTGGGCACCCA 1954 GGGTGCCCACCTGCTTGCCGGCAAGCAGGTGGGCACCC 1955 GGTGCCCACCTGCTTGCCA TGGCAAGCAGGTGGGCACC 1956GTGCCCACCTGCTTGCCAC GTGGCAAGCAGGTGGGCAC 1957 TGCCCACCTGCTTGCCACCGGTGGCAAGCAGGTGGGCA 1958 GCCCACCTGCTTGCCACCC GGGTGGCAAGCAGGTGGGC 1959CCCACCTGCTTGCCACCCT AGGGTGGCAAGCAGGTGGG 1960 CCACCTGCTTGCCACCCTATAGGGTGGCAAGCAGGTGG 1961 CACCTGCTTGCCACCCTAC GTAGGGTGGCAAGCAGGTG 1962ACCTGCTTGCCACCCTACC GGTAGGGTGGCAAGCAGGT 1963 CCTGCTTGCCACCCTACCTAGGTAGGGTGGCAAGCAGG 1964 CTGCTTGCCACCCTACCTA TAGGTAGGGTGGCAAGCAG 1965TGCTTGCCACCCTACCTAG CTAGGTAGGGTGGCAAGCA 1966 GCTTGCCACCCTACCTAGTACTAGGTAGGGTGGCAAGC 1967 CTTGCCACCCTACCTAGTG CACTAGGTAGGGTGGCAAG 1968TTGCCACCCTACCTAGTGT ACACTAGGTAGGGTGGCAA 1969 TGCCACCCTACCTAGTGTCGACACTAGGTAGGGTGGCA 1970 GCCACCCTACCTAGTGTCT AGACACTAGGTAGGGTGGC 1971CCACCCTACCTAGTGTCTG CAGACACTAGGTAGGGTGG 1972 CACCCTACCTAGTGTCTGGCCAGACACTAGGTAGGGTG 1973 ACCCTACCTAGTGTCTGGC GCCAGACACTAGGTAGGGT 1974CCCTACCTAGTGTCTGGCC GGCCAGACACTAGGTAGGG 1975 CCTACCTAGTGTCTGGCCTAGGCCAGACACTAGGTAGG 1976 CTACCTAGTGTCTGGCCTG CAGGCCAGACACTAGGTAG 1977TACCTAGTGTCTGGCCTGC GCAGGCCAGACACTAGGTA 1978 ACCTAGTGTCTGGCCTGCCGGCAGGCCAGACACTAGGT 1979 CCTAGTGTCTGGCCTGCCC GGGCAGGCCAGACACTAGG 1980CTAGTGTCTGGCCTGCCCC GGGGCAGGCCAGACACTAG 1981 TAGTGTCTGGCCTGCCCCCGGGGGCAGGCCAGACACTA 1982 AGTGTCTGGCCTGCCCCCA TGGGGGCAGGCCAGACACT 1983GTGTCTGGCCTGCCCCCAG CTGGGGGCAGGCCAGACAC 1984 TGTCTGGCCTGCCCCCAGATCTGGGGGCAGGCCAGACA 1985 GTCTGGCCTGCCCCCAGAG CTCTGGGGGCAGGCCAGAC 1986TCTGGCCTGCCCCCAGAGC GCTCTGGGGGCAGGCCAGA 1987 CTGGCCTGCCCCCAGAGCATGCTCTGGGGGCAGGCCAG 1988 TGGCCTGCCCCCAGAGCAT ATGCTCTGGGGGCAGGCCA 1989GGCCTGCCCCCAGAGCATC GATGCTCTGGGGGCAGGCC 1990 GCCTGCCCCCAGAGCATCCGGATGCTCTGGGGGCAGGC 1991 CCTGCCCCCAGAGCATCCA TGGATGCTCTGGGGGCAGG 1992CTGCCCCCAGAGCATCCAT ATGGATGCTCTGGGGGCAG 1993 TGCCCCCAGAGCATCCATGCATGGATGCTCTGGGGGCA 1994 GCCCCCAGAGCATCCATGT ACATGGATGCTCTGGGGGC 1995CCCCCAGAGCATCCATGTG CACATGGATGCTCTGGGGG 1996 CCCCAGAGCATCCATGTGATCACATGGATGCTCTGGGG 1997 CCCAGAGCATCCATGTGAC GTCACATGGATGCTCTGGG 1998CCAGAGCATCCATGTGACT AGTCACATGGATGCTCTGG 1999 CAGAGCATCCATGTGACTGCAGTCACATGGATGCTCTG 2000 AGAGCATCCATGTGACTGG CCAGTCACATGGATGCTCT 2001GAGCATCCATGTGACTGGC GCCAGTCACATGGATGCTC 2002 AGCATCCATGTGACTGGCCGGCCAGTCACATGGATGCT 2003 GCATCCATGTGACTGGCCC GGGCCAGTCACATGGATGC 2004CATCCATGTGACTGGCCCC GGGGCCAGTCACATGGATG 2005 ATCCATGTGACTGGCCCCTAGGGGCCAGTCACATGGAT 2006 TCCATGTGACTGGCCCCTG CAGGGGCCAGTCACATGGA 2007CCATGTGACTGGCCCCTGA TCAGGGGCCAGTCACATGG 2008 CATGTGACTGGCCCCTGACGTCAGGGGCCAGTCACATG 2009 ATGTGACTGGCCCCTGACC GGTCAGGGGCCAGTCACAT 2010TGTGACTGGCCCCTGACCC GGGTCAGGGGCCAGTCACA 2011 GTGACTGGCCCCTGACCCCGGGGTCAGGGGCCAGTCAC 2012 TGACTGGCCCCTGACCCCG CGGGGTCAGGGGCCAGTCA 2013GACTGGCCCCTGACCCCGC GCGGGGTCAGGGGCCAGTC 2014 ACTGGCCCCTGACCCCGCATGCGGGGTCAGGGGCCAGT 2015 CTGGCCCCTGACCCCGCAC GTGCGGGGTCAGGGGCCAG 2016TGGCCCCTGACCCCGCACC GGTGCGGGGTCAGGGGCCA 2017 GGCCCCTGACCCCGCACCCGGGTGCGGGGTCAGGGGCC 2018 GCCCCTGACCCCGCACCCC GGGGTGCGGGGTCAGGGGC 2019CCCCTGACCCCGCACCCCT AGGGGTGCGGGGTCAGGGG 2020 CCCTGACCCCGCACCCCTGCAGGGGTGCGGGGTCAGGG 2021 CCTGACCCCGCACCCCTGG CCAGGGGTGCGGGGTCAGG 2022CTGACCCCGCACCCCTGGG CCCAGGGGTGCGGGGTCAG 2023 TGACCCCGCACCCCTGGGTACCCAGGGGTGCGGGGTCA 2024 GACCCCGCACCCCTGGGTA TACCCAGGGGTGCGGGGTC 2025ACCCCGCACCCCTGGGTAT ATACCCAGGGGTGCGGGGT 2026 CCCCGCACCCCTGGGTATATATACCCAGGGGTGCGGGG 2027 CCCGCACCCCTGGGTATAC GTATACCCAGGGGTGCGGG 2028CCGCACCCCTGGGTATACT AGTATACCCAGGGGTGCGG 2029 CGCACCCCTGGGTATACTCGAGTATACCCAGGGGTGCG 2030 GCACCCCTGGGTATACTCC GGAGTATACCCAGGGGTGC 2031CACCCCTGGGTATACTCCG CGGAGTATACCCAGGGGTG 2032 ACCCCTGGGTATACTCCGGCCGGAGTATACCCAGGGGT 2033 CCCCTGGGTATACTCCGGG CCCGGAGTATACCCAGGGG 2034CCCTGGGTATACTCCGGGG CCCCGGAGTATACCCAGGG 2035 CCTGGGTATACTCCGGGGGCCCCCGGAGTATACCCAGG 2036 CTGGGTATACTCCGGGGGC GCCCCCGGAGTATACCCAG 2037TGGGTATACTCCGGGGGCC GGCCCCCGGAGTATACCCA 2038 GGGTATACTCCGGGGGCCATGGCCCCCGGAGTATACCC 2039 GGTATACTCCGGGGGCCAG CTGGCCCCCGGAGTATACC 2040GTATACTCCGGGGGCCAGC GCTGGCCCCCGGAGTATAC 2041 TATACTCCGGGGGCCAGCCGGCTGGCCCCCGGAGTATA 2042 ATACTCCGGGGGCCAGCCC GGGCTGGCCCCCGGAGTAT 2043TACTCCGGGGGCCAGCCCA TGGGCTGGCCCCCGGAGTA 2044 ACTCCGGGGGCCAGCCCAATTGGGCTGGCCCCCGGAGT 2045 CTCCGGGGGCCAGCCCAAA TTTGGGCTGGCCCCCGGAG 2046TCCGGGGGCCAGCCCAAAG CTTTGGGCTGGCCCCCGGA 2047 CCGGGGGCCAGCCCAAAGTACTTTGGGCTGGCCCCCGG 2048 CGGGGGCCAGCCCAAAGTG CACTTTGGGCTGGCCCCCG 2049GGGGGCCAGCCCAAAGTGC GCACTTTGGGCTGGCCCCC 2050 GGGGCCAGCCCAAAGTGCCGGCACTTTGGGCTGGCCCC 2051 GGGCCAGCCCAAAGTGCCC GGGCACTTTGGGCTGGCCC 2052GGCCAGCCCAAAGTGCCCT AGGGCACTTTGGGCTGGCC 2053 GCCAGCCCAAAGTGCCCTCGAGGGCACTTTGGGCTGGC 2054 CCAGCCCAAAGTGCCCTCT AGAGGGCACTTTGGGCTGG 2055CAGCCCAAAGTGCCCTCTG CAGAGGGCACTTTGGGCTG 2056 AGCCCAAAGTGCCCTCTGCGCAGAGGGCACTTTGGGCT 2057 GCCCAAAGTGCCCTCTGCC GGCAGAGGGCACTTTGGGC 2058CCCAAAGTGCCCTCTGCCT AGGCAGAGGGCACTTTGGG 2059 CCAAAGTGCCCTCTGCCTTAAGGCAGAGGGCACTTTGG 2060 CAAAGTGCCCTCTGCCTTC GAAGGCAGAGGGCACTTTG 2061AAAGTGCCCTCTGCCTTCA TGAAGGCAGAGGGCACTTT 2062 AAGTGCCCTCTGCCTTCAGCTGAAGGCAGAGGGCACTT 2063 AGTGCCCTCTGCCTTCAGC GCTGAAGGCAGAGGGCACT 2064GTGCCCTCTGCCTTCAGCT AGCTGAAGGCAGAGGGCAC 2065 TGCCCTCTGCCTTCAGCTTAAGCTGAAGGCAGAGGGCA 2066 GCCCTCTGCCTTCAGCTTA TAAGCTGAAGGCAGAGGGC 2067CCCTCTGCCTTCAGCTTAG CTAAGCTGAAGGCAGAGGG 2068 CCTCTGCCTTCAGCTTAGGCCTAAGCTGAAGGCAGAGG 2069 CTCTGCCTTCAGCTTAGGC GCCTAAGCTGAAGGCAGAG 2070TCTGCCTTCAGCTTAGGCA TGCCTAAGCTGAAGGCAGA 2071 CTGCCTTCAGCTTAGGCAGCTGCCTAAGCTGAAGGCAG 2072 TGCCTTCAGCTTAGGCAGC GCTGCCTAAGCTGAAGGCA 2073GCCTTCAGCTTAGGCAGCA TGCTGCCTAAGCTGAAGGC 2074 CCTTCAGCTTAGGCAGCAATTGCTGCCTAAGCTGAAGG 2075 CTTCAGCTTAGGCAGCAAG CTTGCTGCCTAAGCTGAAG 2076TTCAGCTTAGGCAGCAAGG CCTTGCTGCCTAAGCTGAA 2077 TCAGCTTAGGCAGCAAGGGCCCTTGCTGCCTAAGCTGA 2078 CAGCTTAGGCAGCAAGGGC GCCCTTGCTGCCTAAGCTG 2079AGCTTAGGCAGCAAGGGCT AGCCCTTGCTGCCTAAGCT 2080 GCTTAGGCAGCAAGGGCTTAAGCCCTTGCTGCCTAAGC 2081 CTTAGGCAGCAAGGGCTTT AAAGCCCTTGCTGCCTAAG 2082TTAGGCAGCAAGGGCTTTT AAAAGCCCTTGCTGCCTAA 2083 TAGGCAGCAAGGGCTTTTATAAAAGCCCTTGCTGCCTA 2084 AGGCAGCAAGGGCTTTTAC GTAAAAGCCCTTGCTGCCT 2085GGCAGCAAGGGCTTTTACT AGTAAAAGCCCTTGCTGCC 2086 GCAGCAAGGGCTTTTACTATAGTAAAAGCCCTTGCTGC 2087 CAGCAAGGGCTTTTACTAC GTAGTAAAAGCCCTTGCTG 2088AGCAAGGGCTTTTACTACA TGTAGTAAAAGCCCTTGCT 2089 GCAAGGGCTTTTACTACAATTGTAGTAAAAGCCCTTGC 2090 CAAGGGCTTTTACTACAAG CTTGTAGTAAAAGCCCTTG 2091AAGGGCTTTTACTACAAGG CCTTGTAGTAAAAGCCCTT 2092 AGGGCTTTTACTACAAGGATCCTTGTAGTAAAAGCCCT 2093 GGGCTTTTACTACAAGGAT ATCCTTGTAGTAAAAGCCC 2094GGCTTTTACTACAAGGATC GATCCTTGTAGTAAAAGCC 2095 GCTTTTACTACAAGGATCCGGATCCTTGTAGTAAAAGC 2096 CTTTTACTACAAGGATCCG CGGATCCTTGTAGTAAAAG 2097TTTTACTACAAGGATCCGA TCGGATCCTTGTAGTAAAA 2098 TTTACTACAAGGATCCGAGCTCGGATCCTTGTAGTAAA 2099 TTACTACAAGGATCCGAGC GCTCGGATCCTTGTAGTAA 2100TACTACAAGGATCCGAGCA TGCTCGGATCCTTGTAGTA 2101 ACTACAAGGATCCGAGCATATGCTCGGATCCTTGTAGT 2102 CTACAAGGATCCGAGCATT AATGCTCGGATCCTTGTAG 2103TACAAGGATCCGAGCATTC GAATGCTCGGATCCTTGTA 2104 ACAAGGATCCGAGCATTCCGGAATGCTCGGATCCTTGT 2105 CAAGGATCCGAGCATTCCC GGGAATGCTCGGATCCTTG 2106AAGGATCCGAGCATTCCCA TGGGAATGCTCGGATCCTT 2107 AGGATCCGAGCATTCCCAGCTGGGAATGCTCGGATCCT 2108 GGATCCGAGCATTCCCAGG CCTGGGAATGCTCGGATCC 2109GATCCGAGCATTCCCAGGT ACCTGGGAATGCTCGGATC 2110 ATCCGAGCATTCCCAGGTTAACCTGGGAATGCTCGGAT 2111 TCCGAGCATTCCCAGGTTG CAACCTGGGAATGCTCGGA 2112CCGAGCATTCCCAGGTTGG CCAACCTGGGAATGCTCGG 2113 CGAGCATTCCCAGGTTGGCGCCAACCTGGGAATGCTCG 2114 GAGCATTCCCAGGTTGGCA TGCCAACCTGGGAATGCTC 2115AGCATTCCCAGGTTGGCAA TTGCCAACCTGGGAATGCT 2116 GCATTCCCAGGTTGGCAAATTTGCCAACCTGGGAATGC 2117 CATTCCCAGGTTGGCAAAG CTTTGCCAACCTGGGAATG 2118ATTCCCAGGTTGGCAAAGG CCTTTGCCAACCTGGGAAT 2119 TTCCCAGGTTGGCAAAGGATCCTTTGCCAACCTGGGAA 2120 TCCCAGGTTGGCAAAGGAG CTCCTTTGCCAACCTGGGA 2121CCCAGGTTGGCAAAGGAGC GCTCCTTTGCCAACCTGGG 2122 CCAGGTTGGCAAAGGAGCCGGCTCCTTTGCCAACCTGG 2123 CAGGTTGGCAAAGGAGCCC GGGCTCCTTTGCCAACCTG 2124AGGTTGGCAAAGGAGCCCT AGGGCTCCTTTGCCAACCT 2125 GGTTGGCAAAGGAGCCCTTAAGGGCTCCTTTGCCAACC 2126 GTTGGCAAAGGAGCCCTTG CAAGGGCTCCTTTGCCAAC 2127TTGGCAAAGGAGCCCTTGG CCAAGGGCTCCTTTGCCAA 2128 TGGCAAAGGAGCCCTTGGCGCCAAGGGCTCCTTTGCCA 2129 GGCAAAGGAGCCCTTGGCA TGCCAAGGGCTCCTTTGCC 2130GCAAAGGAGCCCTTGGCAG CTGCCAAGGGCTCCTTTGC 2131 CAAAGGAGCCCTTGGCAGCGCTGCCAAGGGCTCCTTTG 2132 AAAGGAGCCCTTGGCAGCT AGCTGCCAAGGGCTCCTTT 2133AAGGAGCCCTTGGCAGCTG CAGCTGCCAAGGGCTCCTT 2134 AGGAGCCCTTGGCAGCTGCGCAGCTGCCAAGGGCTCCT 2135 GGAGCCCTTGGCAGCTGCG CGCAGCTGCCAAGGGCTCC 2136GAGCCCTTGGCAGCTGCGG CCGCAGCTGCCAAGGGCTC 2137 AGCCCTTGGCAGCTGCGGATCCGCAGCTGCCAAGGGCT 2138 GCCCTTGGCAGCTGCGGAA TTCCGCAGCTGCCAAGGGC 2139CCCTTGGCAGCTGCGGAAC GTTCCGCAGCTGCCAAGGG 2140 CCTTGGCAGCTGCGGAACCGGTTCCGCAGCTGCCAAGG 2141 CTTGGCAGCTGCGGAACCT AGGTTCCGCAGCTGCCAAG 2142TTGGCAGCTGCGGAACCTG CAGGTTCCGCAGCTGCCAA 2143 TGGCAGCTGCGGAACCTGGCCAGGTTCCGCAGCTGCCA 2144 GGCAGCTGCGGAACCTGGG CCCAGGTTCCGCAGCTGCC 2145GCAGCTGCGGAACCTGGGT ACCCAGGTTCCGCAGCTGC 2146 CAGCTGCGGAACCTGGGTTAACCCAGGTTCCGCAGCTG 2147 AGCTGCGGAACCTGGGTTG CAACCCAGGTTCCGCAGCT 2148GCTGCGGAACCTGGGTTGT ACAACCCAGGTTCCGCAGC 2149 CTGCGGAACCTGGGTTGTTAACAACCCAGGTTCCGCAG 2150 TGCGGAACCTGGGTTGTTT AAACAACCCAGGTTCCGCA 2151GCGGAACCTGGGTTGTTTG CAAACAACCCAGGTTCCGC 2152 CGGAACCTGGGTTGTTTGGCCAAACAACCCAGGTTCCG 2153 GGAACCTGGGTTGTTTGGC GCCAAACAACCCAGGTTCC 2154GAACCTGGGTTGTTTGGCT AGCCAAACAACCCAGGTTC 2155 AACCTGGGTTGTTTGGCTTAAGCCAAACAACCCAGGTT 2156 ACCTGGGTTGTTTGGCTTA TAAGCCAAACAACCCAGGT 2157CCTGGGTTGTTTGGCTTAA TTAAGCCAAACAACCCAGG 2158 CTGGGTTGTTTGGCTTAAATTTAAGCCAAACAACCCAG 2159 TGGGTTGTTTGGCTTAAAC GTTTAAGCCAAACAACCCA 2160GGGTTGTTTGGCTTAAACT AGTTTAAGCCAAACAACCC 2161 GGTTGTTTGGCTTAAACTCGAGTTTAAGCCAAACAACC 2162 GTTGTTTGGCTTAAACTCT AGAGTTTAAGCCAAACAAC 2163TTGTTTGGCTTAAACTCTG CAGAGTTTAAGCCAAACAA 2164 TGTTTGGCTTAAACTCTGGCCAGAGTTTAAGCCAAACA 2165 GTTTGGCTTAAACTCTGGT ACCAGAGTTTAAGCCAAAC 2166TTTGGCTTAAACTCTGGTG CACCAGAGTTTAAGCCAAA 2167 TTGGCTTAAACTCTGGTGGCCACCAGAGTTTAAGCCAA 2168 TGGCTTAAACTCTGGTGGG CCCACCAGAGTTTAAGCCA 2169GGCTTAAACTCTGGTGGGC GCCCACCAGAGTTTAAGCC 2170 GCTTAAACTCTGGTGGGCATGCCCACCAGAGTTTAAGC 2171 CTTAAACTCTGGTGGGCAC GTGCCCACCAGAGTTTAAG 2172TTAAACTCTGGTGGGCACC GGTGCCCACCAGAGTTTAA 2173 TAAACTCTGGTGGGCACCTAGGTGCCCACCAGAGTTTA 2174 AAACTCTGGTGGGCACCTG CAGGTGCCCACCAGAGTTT 2175AACTCTGGTGGGCACCTGC GCAGGTGCCCACCAGAGTT 2176 ACTCTGGTGGGCACCTGCATGCAGGTGCCCACCAGAGT 2177 CTCTGGTGGGCACCTGCAG CTGCAGGTGCCCACCAGAG 2178TCTGGTGGGCACCTGCAGA TCTGCAGGTGCCCACCAGA 2179 CTGGTGGGCACCTGCAGAGCTCTGCAGGTGCCCACCAG 2180 TGGTGGGCACCTGCAGAGA TCTCTGCAGGTGCCCACCA 2181GGTGGGCACCTGCAGAGAG CTCTCTGCAGGTGCCCACC 2182 GTGGGCACCTGCAGAGAGCGCTCTCTGCAGGTGCCCAC 2183 TGGGCACCTGCAGAGAGCC GGCTCTCTGCAGGTGCCCA 2184GGGCACCTGCAGAGAGCCG CGGCTCTCTGCAGGTGCCC 2185 GGCACCTGCAGAGAGCCGGCCGGCTCTCTGCAGGTGCC 2186 GCACCTGCAGAGAGCCGGG CCCGGCTCTCTGCAGGTGC 2187CACCTGCAGAGAGCCGGGG CCCCGGCTCTCTGCAGGTG 2188 ACCTGCAGAGAGCCGGGGATCCCCGGCTCTCTGCAGGT 2189 CCTGCAGAGAGCCGGGGAG CTCCCCGGCTCTCTGCAGG 2190CTGCAGAGAGCCGGGGAGG CCTCCCCGGCTCTCTGCAG 2191 TGCAGAGAGCCGGGGAGGCGCCTCCCCGGCTCTCTGCA 2192 GCAGAGAGCCGGGGAGGCC GGCCTCCCCGGCTCTCTGC 2193CAGAGAGCCGGGGAGGCCG CGGCCTCCCCGGCTCTCTG 2194 AGAGAGCCGGGGAGGCCGATCGGCCTCCCCGGCTCTCT 2195 GAGAGCCGGGGAGGCCGAA TTCGGCCTCCCCGGCTCTC 2196AGAGCCGGGGAGGCCGAAC GTTCGGCCTCCCCGGCTCT 2197 GAGCCGGGGAGGCCGAACGCGTTCGGCCTCCCCGGCTC 2198 AGCCGGGGAGGCCGAACGC GCGTTCGGCCTCCCCGGCT 2199GCCGGGGAGGCCGAACGCC GGCGTTCGGCCTCCCCGGC 2200 CCGGGGAGGCCGAACGCCCGGGCGTTCGGCCTCCCCGG 2201 CGGGGAGGCCGAACGCCCT AGGGCGTTCGGCCTCCCCG 2202GGGGAGGCCGAACGCCCTT AAGGGCGTTCGGCCTCCCC 2203 GGGAGGCCGAACGCCCTTCGAAGGGCGTTCGGCCTCCC 2204 GGAGGCCGAACGCCCTTCA TGAAGGGCGTTCGGCCTCC 2205GAGGCCGAACGCCCTTCAC GTGAAGGGCGTTCGGCCTC 2206 AGGCCGAACGCCCTTCACTAGTGAAGGGCGTTCGGCCT 2207 GGCCGAACGCCCTTCACTG CAGTGAAGGGCGTTCGGCC 2208GCCGAACGCCCTTCACTGC GCAGTGAAGGGCGTTCGGC 2209 CCGAACGCCCTTCACTGCATGCAGTGAAGGGCGTTCGG 2210 CGAACGCCCTTCACTGCAC GTGCAGTGAAGGGCGTTCG 2211GAACGCCCTTCACTGCACC GGTGCAGTGAAGGGCGTTC 2212 AACGCCCTTCACTGCACCATGGTGCAGTGAAGGGCGTT 2213 ACGCCCTTCACTGCACCAG CTGGTGCAGTGAAGGGCGT 2214CGCCCTTCACTGCACCAGA TCTGGTGCAGTGAAGGGCG 2215 GCCCTTCACTGCACCAGAGCTCTGGTGCAGTGAAGGGC 2216 CCCTTCACTGCACCAGAGG CCTCTGGTGCAGTGAAGGG 2217CCTTCACTGCACCAGAGGG CCCTCTGGTGCAGTGAAGG 2218 CTTCACTGCACCAGAGGGATCCCTCTGGTGCAGTGAAG 2219 TTCACTGCACCAGAGGGAT ATCCCTCTGGTGCAGTGAA 2220TCACTGCACCAGAGGGATG CATCCCTCTGGTGCAGTGA 2221 CACTGCACCAGAGGGATGGCCATCCCTCTGGTGCAGTG 2222 ACTGCACCAGAGGGATGGA TCCATCCCTCTGGTGCAGT 2223CTGCACCAGAGGGATGGAG CTCCATCCCTCTGGTGCAG 2224 TGCACCAGAGGGATGGAGATCTCCATCCCTCTGGTGCA 2225 GCACCAGAGGGATGGAGAG CTCTCCATCCCTCTGGTGC 2226CACCAGAGGGATGGAGAGA TCTCTCCATCCCTCTGGTG 2227 ACCAGAGGGATGGAGAGATATCTCTCCATCCCTCTGGT 2228 CCAGAGGGATGGAGAGATG CATCTCTCCATCCCTCTGG 2229CAGAGGGATGGAGAGATGG CCATCTCTCCATCCCTCTG 2230 AGAGGGATGGAGAGATGGGCCCATCTCTCCATCCCTCT 2231 GAGGGATGGAGAGATGGGA TCCCATCTCTCCATCCCTC 2232AGGGATGGAGAGATGGGAG CTCCCATCTCTCCATCCCT 2233 GGGATGGAGAGATGGGAGCGCTCCCATCTCTCCATCCC 2234 GGATGGAGAGATGGGAGCT AGCTCCCATCTCTCCATCC 2235GATGGAGAGATGGGAGCTG CAGCTCCCATCTCTCCATC 2236 ATGGAGAGATGGGAGCTGGCCAGCTCCCATCTCTCCAT 2237 TGGAGAGATGGGAGCTGGC GCCAGCTCCCATCTCTCCA 2238GGAGAGATGGGAGCTGGCC GGCCAGCTCCCATCTCTCC 2239 GAGAGATGGGAGCTGGCCGCGGCCAGCTCCCATCTCTC 2240 AGAGATGGGAGCTGGCCGG CCGGCCAGCTCCCATCTCT 2241GAGATGGGAGCTGGCCGGC GCCGGCCAGCTCCCATCTC 2242 AGATGGGAGCTGGCCGGCATGCCGGCCAGCTCCCATCT 2243 GATGGGAGCTGGCCGGCAG CTGCCGGCCAGCTCCCATC 2244ATGGGAGCTGGCCGGCAGC GCTGCCGGCCAGCTCCCAT 2245 TGGGAGCTGGCCGGCAGCATGCTGCCGGCCAGCTCCCA 2246 GGGAGCTGGCCGGCAGCAG CTGCTGCCGGCCAGCTCCC 2247GGAGCTGGCCGGCAGCAGA TCTGCTGCCGGCCAGCTCC 2248 GAGCTGGCCGGCAGCAGAATTCTGCTGCCGGCCAGCTC 2249 AGCTGGCCGGCAGCAGAAT ATTCTGCTGCCGGCCAGCT 2250GCTGGCCGGCAGCAGAATC GATTCTGCTGCCGGCCAGC 2251 CTGGCCGGCAGCAGAATCCGGATTCTGCTGCCGGCCAG 2252 TGGCCGGCAGCAGAATCCT AGGATTCTGCTGCCGGCCA 2253GGCCGGCAGCAGAATCCTT AAGGATTCTGCTGCCGGCC 2254 GCCGGCAGCAGAATCCTTGCAAGGATTCTGCTGCCGGC 2255 CCGGCAGCAGAATCCTTGC GCAAGGATTCTGCTGCCGG 2256CGGCAGCAGAATCCTTGCC GGCAAGGATTCTGCTGCCG 2257 GGCAGCAGAATCCTTGCCCGGGCAAGGATTCTGCTGCC 2258 GCAGCAGAATCCTTGCCCG CGGGCAAGGATTCTGCTGC 2259CAGCAGAATCCTTGCCCGC GCGGGCAAGGATTCTGCTG 2260 AGCAGAATCCTTGCCCGCTAGCGGGCAAGGATTCTGCT 2261 GCAGAATCCTTGCCCGCTC GAGCGGGCAAGGATTCTGC 2262CAGAATCCTTGCCCGCTCT AGAGCGGGCAAGGATTCTG 2263 AGAATCCTTGCCCGCTCTTAAGAGCGGGCAAGGATTCT 2264 GAATCCTTGCCCGCTCTTC GAAGAGCGGGCAAGGATTC 2265AATCCTTGCCCGCTCTTCC GGAAGAGCGGGCAAGGATT 2266 ATCCTTGCCCGCTCTTCCTAGGAAGAGCGGGCAAGGAT 2267 TCCTTGCCCGCTCTTCCTG CAGGAAGAGCGGGCAAGGA 2268CCTTGCCCGCTCTTCCTGG CCAGGAAGAGCGGGCAAGG 2269 CTTGCCCGCTCTTCCTGGGCCCAGGAAGAGCGGGCAAG 2270 TTGCCCGCTCTTCCTGGGG CCCCAGGAAGAGCGGGCAA 2271TGCCCGCTCTTCCTGGGGC GCCCCAGGAAGAGCGGGCA 2272 GCCCGCTCTTCCTGGGGCATGCCCCAGGAAGAGCGGGC 2273 CCCGCTCTTCCTGGGGCAG CTGCCCCAGGAAGAGCGGG 2274CCGCTCTTCCTGGGGCAGC GCTGCCCCAGGAAGAGCGG 2275 CGCTCTTCCTGGGGCAGCCGGCTGCCCCAGGAAGAGCG 2276 GCTCTTCCTGGGGCAGCCA TGGCTGCCCCAGGAAGAGC 2277CTCTTCCTGGGGCAGCCAG CTGGCTGCCCCAGGAAGAG 2278 TCTTCCTGGGGCAGCCAGATCTGGCTGCCCCAGGAAGA 2279 CTTCCTGGGGCAGCCAGAC GTCTGGCTGCCCCAGGAAG 2280TTCCTGGGGCAGCCAGACA TGTCTGGCTGCCCCAGGAA 2281 TCCTGGGGCAGCCAGACACGTGTCTGGCTGCCCCAGGA 2282 CCTGGGGCAGCCAGACACT AGTGTCTGGCTGCCCCAGG 2283CTGGGGCAGCCAGACACTG CAGTGTCTGGCTGCCCCAG 2284 TGGGGCAGCCAGACACTGTACAGTGTCTGGCTGCCCCA 2285 GGGGCAGCCAGACACTGTG CACAGTGTCTGGCTGCCCC 2286GGGCAGCCAGACACTGTGC GCACAGTGTCTGGCTGCCC 2287 GGCAGCCAGACACTGTGCCGGCACAGTGTCTGGCTGCC 2288 GCAGCCAGACACTGTGCCC GGGCACAGTGTCTGGCTGC 2289CAGCCAGACACTGTGCCCT AGGGCACAGTGTCTGGCTG 2290 AGCCAGACACTGTGCCCTGCAGGGCACAGTGTCTGGCT 2291 GCCAGACACTGTGCCCTGG CCAGGGCACAGTGTCTGGC 2292CCAGACACTGTGCCCTGGA TCCAGGGCACAGTGTCTGG 2293 CAGACACTGTGCCCTGGACGTCCAGGGCACAGTGTCTG 2294 AGACACTGTGCCCTGGACC GGTCCAGGGCACAGTGTCT 2295GACACTGTGCCCTGGACCT AGGTCCAGGGCACAGTGTC 2296 ACACTGTGCCCTGGACCTCGAGGTCCAGGGCACAGTGT 2297 CACTGTGCCCTGGACCTCC GGAGGTCCAGGGCACAGTG 2298ACTGTGCCCTGGACCTCCT AGGAGGTCCAGGGCACAGT 2299 CTGTGCCCTGGACCTCCTGCAGGAGGTCCAGGGCACAG 2300 TGTGCCCTGGACCTCCTGG CCAGGAGGTCCAGGGCACA 2301GTGCCCTGGACCTCCTGGC GCCAGGAGGTCCAGGGCAC 2302 TGCCCTGGACCTCCTGGCCGGCCAGGAGGTCCAGGGCA 2303 GCCCTGGACCTCCTGGCCC GGGCCAGGAGGTCCAGGGC 2304CCCTGGACCTCCTGGCCCG CGGGCCAGGAGGTCCAGGG 2305 CCTGGACCTCCTGGCCCGCGCGGGCCAGGAGGTCCAGG 2306 CTGGACCTCCTGGCCCGCT AGCGGGCCAGGAGGTCCAG 2307TGGACCTCCTGGCCCGCTT AAGCGGGCCAGGAGGTCCA 2308 GGACCTCCTGGCCCGCTTGCAAGCGGGCCAGGAGGTCC 2309 GACCTCCTGGCCCGCTTGT ACAAGCGGGCCAGGAGGTC 2310ACCTCCTGGCCCGCTTGTC GACAAGCGGGCCAGGAGGT 2311 CCTCCTGGCCCGCTTGTCCGGACAAGCGGGCCAGGAGG 2312 CTCCTGGCCCGCTTGTCCC GGGACAAGCGGGCCAGGAG 2313TCCTGGCCCGCTTGTCCCC GGGGACAAGCGGGCCAGGA 2314 CCTGGCCCGCTTGTCCCCCGGGGGACAAGCGGGCCAGG 2315 CTGGCCCGCTTGTCCCCCA TGGGGGACAAGCGGGCCAG 2316TGGCCCGCTTGTCCCCCAG CTGGGGGACAAGCGGGCCA 2317 GGCCCGCTTGTCCCCCAGGCCTGGGGGACAAGCGGGCC 2318 GCCCGCTTGTCCCCCAGGC GCCTGGGGGACAAGCGGGC 2319CCCGCTTGTCCCCCAGGCC GGCCTGGGGGACAAGCGGG 2320 CCGCTTGTCCCCCAGGCCTAGGCCTGGGGGACAAGCGG 2321 CGCTTGTCCCCCAGGCCTT AAGGCCTGGGGGACAAGCG 2322GCTTGTCCCCCAGGCCTTG CAAGGCCTGGGGGACAAGC 2323 CTTGTCCCCCAGGCCTTGTACAAGGCCTGGGGGACAAG 2324 TTGTCCCCCAGGCCTTGTT AACAAGGCCTGGGGGACAA 2325TGTCCCCCAGGCCTTGTTC GAACAAGGCCTGGGGGACA 2326 GTCCCCCAGGCCTTGTTCATGAACAAGGCCTGGGGGAC 2327 TCCCCCAGGCCTTGTTCAT ATGAACAAGGCCTGGGGGA 2328CCCCCAGGCCTTGTTCATA TATGAACAAGGCCTGGGGG 2329 CCCCAGGCCTTGTTCATACGTATGAACAAGGCCTGGGG 2330 CCCAGGCCTTGTTCATACT AGTATGAACAAGGCCTGGG 2331CCAGGCCTTGTTCATACTC GAGTATGAACAAGGCCTGG 2332 CAGGCCTTGTTCATACTCTAGAGTATGAACAAGGCCTG 2333 AGGCCTTGTTCATACTCTT AAGAGTATGAACAAGGCCT 2334GGCCTTGTTCATACTCTTG CAAGAGTATGAACAAGGCC 2335 GCCTTGTTCATACTCTTGGCCAAGAGTATGAACAAGGC 2336 CCTTGTTCATACTCTTGGC GCCAAGAGTATGAACAAGG 2337CTTGTTCATACTCTTGGCA TGCCAAGAGTATGAACAAG 2338 TTGTTCATACTCTTGGCAATTGCCAAGAGTATGAACAA 2339 TGTTCATACTCTTGGCAAC GTTGCCAAGAGTATGAACA 2340GTTCATACTCTTGGCAACG CGTTGCCAAGAGTATGAAC 2341 TTCATACTCTTGGCAACGTACGTTGCCAAGAGTATGAA 2342 TCATACTCTTGGCAACGTC GACGTTGCCAAGAGTATGA 2343CATACTCTTGGCAACGTCT AGACGTTGCCAAGAGTATG 2344 ATACTCTTGGCAACGTCTGCAGACGTTGCCAAGAGTAT 2345 TACTCTTGGCAACGTCTGG CCAGACGTTGCCAAGAGTA 2346ACTCTTGGCAACGTCTGGG CCCAGACGTTGCCAAGAGT 2347 CTCTTGGCAACGTCTGGGCGCCCAGACGTTGCCAAGAG 2348 TCTTGGCAACGTCTGGGCT AGCCCAGACGTTGCCAAGA 2349CTTGGCAACGTCTGGGCTG CAGCCCAGACGTTGCCAAG 2350 TTGGCAACGTCTGGGCTGGCCAGCCCAGACGTTGCCAA 2351 TGGCAACGTCTGGGCTGGG CCCAGCCCAGACGTTGCCA 2352GGCAACGTCTGGGCTGGGC GCCCAGCCCAGACGTTGCC 2353 GCAACGTCTGGGCTGGGCCGGCCCAGCCCAGACGTTGC 2354 CAACGTCTGGGCTGGGCCA TGGCCCAGCCCAGACGTTG 2355AACGTCTGGGCTGGGCCAG CTGGCCCAGCCCAGACGTT 2356 ACGTCTGGGCTGGGCCAGGCCTGGCCCAGCCCAGACGT 2357 CGTCTGGGCTGGGCCAGGC GCCTGGCCCAGCCCAGACG 2358GTCTGGGCTGGGCCAGGCG CGCCTGGCCCAGCCCAGAC 2359 TCTGGGCTGGGCCAGGCGATCGCCTGGCCCAGCCCAGA 2360 CTGGGCTGGGCCAGGCGAT ATCGCCTGGCCCAGCCCAG 2361TGGGCTGGGCCAGGCGATG CATCGCCTGGCCCAGCCCA 2362 GGGCTGGGCCAGGCGATGGCCATCGCCTGGCCCAGCCC 2363 GGCTGGGCCAGGCGATGGG CCCATCGCCTGGCCCAGCC 2364GCTGGGCCAGGCGATGGGA TCCCATCGCCTGGCCCAGC 2365 CTGGGCCAGGCGATGGGAATTCCCATCGCCTGGCCCAG 2366 TGGGCCAGGCGATGGGAAC GTTCCCATCGCCTGGCCCA 2367GGGCCAGGCGATGGGAACC GGTTCCCATCGCCTGGCCC 2368 GGCCAGGCGATGGGAACCTAGGTTCCCATCGCCTGGCC 2369 GCCAGGCGATGGGAACCTT AAGGTTCCCATCGCCTGGC 2370CCAGGCGATGGGAACCTTG CAAGGTTCCCATCGCCTGG 2371 CAGGCGATGGGAACCTTGGCCAAGGTTCCCATCGCCTG 2372 AGGCGATGGGAACCTTGGG CCCAAGGTTCCCATCGCCT 2373GGCGATGGGAACCTTGGGT ACCCAAGGTTCCCATCGCC 2374 GCGATGGGAACCTTGGGTATACCCAAGGTTCCCATCGC 2375 CGATGGGAACCTTGGGTAC GTACCCAAGGTTCCCATCG 2376GATGGGAACCTTGGGTACC GGTACCCAAGGTTCCCATC 2377 ATGGGAACCTTGGGTACCATGGTACCCAAGGTTCCCAT 2378 TGGGAACCTTGGGTACCAG CTGGTACCCAAGGTTCCCA 2379GGGAACCTTGGGTACCAGC GCTGGTACCCAAGGTTCCC 2380 GGAACCTTGGGTACCAGCTAGCTGGTACCCAAGGTTCC 2381 GAACCTTGGGTACCAGCTG CAGCTGGTACCCAAGGTTC 2382AACCTTGGGTACCAGCTGG CCAGCTGGTACCCAAGGTT 2383 ACCTTGGGTACCAGCTGGGCCCAGCTGGTACCCAAGGT 2384 CCTTGGGTACCAGCTGGGG CCCCAGCTGGTACCCAAGG 2385CTTGGGTACCAGCTGGGGC GCCCCAGCTGGTACCCAAG 2386 TTGGGTACCAGCTGGGGCCGGCCCCAGCTGGTACCCAA 2387 TGGGTACCAGCTGGGGCCA TGGCCCCAGCTGGTACCCA 2388GGGTACCAGCTGGGGCCAC GTGGCCCCAGCTGGTACCC 2389 GGTACCAGCTGGGGCCACCGGTGGCCCCAGCTGGTACC 2390 GTACCAGCTGGGGCCACCA TGGTGGCCCCAGCTGGTAC 2391TACCAGCTGGGGCCACCAG CTGGTGGCCCCAGCTGGTA 2392 ACCAGCTGGGGCCACCAGCGCTGGTGGCCCCAGCTGGT 2393 CCAGCTGGGGCCACCAGCA TGCTGGTGGCCCCAGCTGG 2394CAGCTGGGGCCACCAGCAA TTGCTGGTGGCCCCAGCTG 2395 AGCTGGGGCCACCAGCAACGTTGCTGGTGGCCCCAGCT 2396 GCTGGGGCCACCAGCAACA TGTTGCTGGTGGCCCCAGC 2397CTGGGGCCACCAGCAACAC GTGTTGCTGGTGGCCCCAG 2398 TGGGGCCACCAGCAACACCGGTGTTGCTGGTGGCCCCA 2399 GGGGCCACCAGCAACACCA TGGTGTTGCTGGTGGCCCC 2400GGGCCACCAGCAACACCAA TTGGTGTTGCTGGTGGCCC 2401 GGCCACCAGCAACACCAAGCTTGGTGTTGCTGGTGGCC 2402 GCCACCAGCAACACCAAGG CCTTGGTGTTGCTGGTGGC 2403CCACCAGCAACACCAAGGT ACCTTGGTGTTGCTGGTGG 2404 CACCAGCAACACCAAGGTGCACCTTGGTGTTGCTGGTG 2405 ACCAGCAACACCAAGGTGC GCACCTTGGTGTTGCTGGT 2406CCAGCAACACCAAGGTGCC GGCACCTTGGTGTTGCTGG 2407 CAGCAACACCAAGGTGCCCGGGCACCTTGGTGTTGCTG 2408 AGCAACACCAAGGTGCCCC GGGGCACCTTGGTGTTGCT 2409GCAACACCAAGGTGCCCCT AGGGGCACCTTGGTGTTGC 2410 CAACACCAAGGTGCCCCTCGAGGGGCACCTTGGTGTTG 2411 AACACCAAGGTGCCCCTCT AGAGGGGCACCTTGGTGTT 2412ACACCAAGGTGCCCCTCTC GAGAGGGGCACCTTGGTGT 2413 CACCAAGGTGCCCCTCTCCGGAGAGGGGCACCTTGGTG 2414 ACCAAGGTGCCCCTCTCCT AGGAGAGGGGCACCTTGGT 2415CCAAGGTGCCCCTCTCCTG CAGGAGAGGGGCACCTTGG 2416 CAAGGTGCCCCTCTCCTGATCAGGAGAGGGGCACCTTG 2417 AAGGTGCCCCTCTCCTGAG CTCAGGAGAGGGGCACCTT 2418AGGTGCCCCTCTCCTGAGC GCTCAGGAGAGGGGCACCT 2419 GGTGCCCCTCTCCTGAGCCGGCTCAGGAGAGGGGCACC 2420 GTGCCCCTCTCCTGAGCCG CGGCTCAGGAGAGGGGCAC 2421TGCCCCTCTCCTGAGCCGC GCGGCTCAGGAGAGGGGCA 2422 GCCCCTCTCCTGAGCCGCCGGCGGCTCAGGAGAGGGGC 2423 CCCCTCTCCTGAGCCGCCT AGGCGGCTCAGGAGAGGGG 2424CCCTCTCCTGAGCCGCCTG CAGGCGGCTCAGGAGAGGG 2425 CCTCTCCTGAGCCGCCTGTACAGGCGGCTCAGGAGAGG 2426 CTCTCCTGAGCCGCCTGTC GACAGGCGGCTCAGGAGAG 2427TCTCCTGAGCCGCCTGTCA TGACAGGCGGCTCAGGAGA 2428 CTCCTGAGCCGCCTGTCACGTGACAGGCGGCTCAGGAG 2429 TCCTGAGCCGCCTGTCACC GGTGACAGGCGGCTCAGGA 2430CCTGAGCCGCCTGTCACCC GGGTGACAGGCGGCTCAGG 2431 CTGAGCCGCCTGTCACCCATGGGTGACAGGCGGCTCAG 2432 TGAGCCGCCTGTCACCCAG CTGGGTGACAGGCGGCTCA 2433GAGCCGCCTGTCACCCAGC GCTGGGTGACAGGCGGCTC 2434 AGCCGCCTGTCACCCAGCGCGCTGGGTGACAGGCGGCT 2435 GCCGCCTGTCACCCAGCGG CCGCTGGGTGACAGGCGGC 2436CCGCCTGTCACCCAGCGGG CCCGCTGGGTGACAGGCGG 2437 CGCCTGTCACCCAGCGGGGCCCCGCTGGGTGACAGGCG 2438 GCCTGTCACCCAGCGGGGC GCCCCGCTGGGTGACAGGC 2439CCTGTCACCCAGCGGGGCT AGCCCCGCTGGGTGACAGG 2440 CTGTCACCCAGCGGGGCTGCAGCCCCGCTGGGTGACAG 2441 TGTCACCCAGCGGGGCTGC GCAGCCCCGCTGGGTGACA 2442GTCACCCAGCGGGGCTGCT AGCAGCCCCGCTGGGTGAC 2443 TCACCCAGCGGGGCTGCTGCAGCAGCCCCGCTGGGTGA 2444 CACCCAGCGGGGCTGCTGT ACAGCAGCCCCGCTGGGTG 2445ACCCAGCGGGGCTGCTGTT AACAGCAGCCCCGCTGGGT 2446 CCCAGCGGGGCTGCTGTTCGAACAGCAGCCCCGCTGGG 2447 CCAGCGGGGCTGCTGTTCA TGAACAGCAGCCCCGCTGG 2448CAGCGGGGCTGCTGTTCAT ATGAACAGCAGCCCCGCTG 2449 AGCGGGGCTGCTGTTCATCGATGAACAGCAGCCCCGCT 2450 GCGGGGCTGCTGTTCATCC GGATGAACAGCAGCCCCGC 2451CGGGGCTGCTGTTCATCCT AGGATGAACAGCAGCCCCG 2452 GGGGCTGCTGTTCATCCTATAGGATGAACAGCAGCCCC 2453 GGGCTGCTGTTCATCCTAC GTAGGATGAACAGCAGCCC 2454GGCTGCTGTTCATCCTACC GGTAGGATGAACAGCAGCC 2455 GCTGCTGTTCATCCTACCCGGGTAGGATGAACAGCAGC 2456 CTGCTGTTCATCCTACCCA TGGGTAGGATGAACAGCAG 2457TGCTGTTCATCCTACCCAC GTGGGTAGGATGAACAGCA 2458 GCTGTTCATCCTACCCACCGGTGGGTAGGATGAACAGC 2459 CTGTTCATCCTACCCACCC GGGTCGGTAGGATGAACAG 2460TGTTCATCCTACCCACCCA TGGGTGGGTAGGATGAACA 2461 GTTCATCCTACCCACCCACGTGGGTGGGTAGGATGAAC 2462 TTCATCCTACCCACCCACT AGTGGGTGGGTAGGATGAA 2463TCATCCTACCCACCCACTA TAGTGGGTGGGTAGGATGA 2464 CATCCTACCCACCCACTAATTAGTGGGTGGGTAGGATG 2465 ATCCTACCCACCCACTAAA TTTAGTGGGTGGGTAGGAT 2466TCCTACCCACCCACTAAAG CTTTAGTGGGTGGGTAGGA 2467 CCTACCCACCCACTAAAGGCCTTTAGTGGGTGGGTAGG 2468 CTACCCACCCACTAAAGGT ACCTTTAGTGGGTGGGTAG 2469TACCCACCCACTAAAGGTG CACCTTTAGTGGGTGGGTA 2470 ACCCACCCACTAAAGGTGGCCACCTTTAGTGGGTGGGT 2471 CCCACCCACTAAAGGTGGG CCCACCTTTAGTGGGTGGG 2472CCACCCACTAAAGGTGGGG CCCCACCTTTAGTGGGTGG 2473 CACCCACTAAAGGTGGGGGCCCCCACCTTTAGTGGGTG 2474 ACCCACTAAAGGTGGGGGT ACCCCCACCTTTAGTGGGT 2475CCCACTAAAGGTGGGGGTC GACCCCCACCTTTAGTGGG 2476 CCACTAAAGGTGGGGGTCTAGACCCCCACCTTTAGTGG 2477 CACTAAAGGTGGGGGTCTT AAGACCCCCACCTTTAGTG 2478ACTAAAGGTGGGGGTCTTG CAAGACCCCCACCTTTAGT 2479 CTAAAGGTGGGGGTCTTGGCCAAGACCCCCACCTTTAG 2480 TAAAGGTGGGGGTCTTGGC GCCAAGACCCCCACCTTTA 2481AAAGGTGGGGGTCTTGGCC GGCCAAGACCCCCACCTTT 2482 AAGGTGGGGGTCTTGGCCCGGGCCAAGACCCCCACCTT 2483 AGGTGGGGGTCTTGGCCCT AGGGCCAAGACCCCCACCT 2484GGTGGGGGTCTTGGCCCTT AAGGGCCAAGACCCCCACC 2485 GTGGGGGTCTTGGCCCTTGCAAGGGCCAAGACCCCCAC 2486 TGGGGGTCTTGGCCCTTGT ACAAGGGCCAAGACCCCCA 2487GGGGGTCTTGGCCCTTGTG CACAAGGGCCAAGACCCCC 2488 GGGGTCTTGGCCCTTGTGGCCACAAGGGCCAAGACCCC 2489 GGGTCTTGGCCCTTGTGGG CCCACAAGGGCCAAGACCC 2490GGTCTTGGCCCTTGTGGGA TCCCACAAGGGCCAAGACC 2491 GTCTTGGCCCTTGTGGGAATTCCCACAAGGGCCAAGAC 2492 TCTTGGCCCTTGTGGGAAG CTTCCCACAAGGGCCAAGA 2493CTTGGCCCTTGTGGGAAGT ACTTCCCACAAGGGCCAAG 2494 TTGGCCCTTGTGGGAAGTGCACTTCCCACAAGGGCCAA 2495 TGGCCCTTGTGGGAAGTGC GCACTTCCCACAAGGGCCA 2496GGCCCTTGTGGGAAGTGCC GGCACTTCCCACAAGGGCC 2497 GCCCTTGTGGGAAGTGCCATGGCACTTCCCACAAGGGC 2498 CCCTTGTGGGAAGTGCCAG CTGGCACTTCCCACAAGGG 2499CCTTGTGGGAAGTGCCAGG CCTGGCACTTCCCACAAGG 2500 CTTGTGGGAAGTGCCAGGATCCTGGCACTTCCCACAAG 2501 TTGTGGGAAGTGCCAGGAG CTCCTGGCACTTCCCACAA 2502TGTGGGAAGTGCCAGGAGG CCTCCTGGCACTTCCCACA 2503 GTGGGAAGTGCCAGGAGGGCCCTCCTGGCACTTCCCAC 2504 TGGGAAGTGCCAGGAGGGC GCCCTCCTGGCACTTCCCA 2505GGGAAGTGCCAGGAGGGCC GGCCCTCCTGGCACTTCCC 2506 GGAAGTGCCAGGAGGGCCTAGGCCCTCCTGGCACTTCC 2507 GAAGTGCCAGGAGGGCCTG CAGGCCCTCCTGGCACTTC 2508AAGTGCCAGGAGGGCCTGG CCAGGCCCTCCTGGCACTT 2509 AGTGCCAGGAGGGCCTGGATCCAGGCCCTCCTGGCACT 2510 GTGCCAGGAGGGCCTGGAG CTCCAGGCCCTCCTGGCAC 2511TGCCAGGAGGGCCTGGAGG CCTCCAGGCCCTCCTGGCA 2512 GCCAGGAGGGCCTGGAGGGCCCTCCAGGCCCTCCTGGC 2513 CCAGGAGGGCCTGGAGGGG CCCCTCCAGGCCCTCCTGG 2514CAGGAGGGCCTGGAGGGGG CCCCCTCCAGGCCCTCCTG 2515 AGGAGGGCCTGGAGGGGGGCCCCCCTCCAGGCCCTCCT 2516 GGAGGGCCTGGAGGGGGGT ACCCCCCTCCAGGCCCTCC 2517GAGGGCCTGGAGGGGGGTG CACCCCCCTCCAGGCCCTC 2518 AGGGCCTGGAGGGGGGTGCGCACCCCCCTCCAGGCCCT 2519 GGGCCTGGAGGGGGGTGCC GGCACCCCCCTCCAGGCCC 2520GGCCTGGAGGGGGGTGCCA TGGCACCCCCCTCCAGGCC 2521 GCCTGGAGGGGGGTGCCAGCTGGCACCCCCCTCCAGGC 2522 CCTGGAGGGGGGTGCCAGT ACTGGCACCCCCCTCCAGG 2523CTGGAGGGGGGTGCCAGTG CACTGGCACCCCCCTCCAG 2524 TGGAGGGGGGTGCCAGTGGCCACTGGCACCCCCCTCCA 2525 GGAGGGGGGTGCCAGTGGA TCCACTGGCACCCCCCTCC 2526GAGGGGGGTGCCAGTGGAG CTCCACTGGCACCCCCCTC 2527 AGGGGGGTGCCAGTGGAGCGCTCCACTGGCACCCCCCT 2528 GGGGGGTGCCAGTGGAGCC GGCTCCACTGGCACCCCCC 2529GGGGGTGCCAGTGGAGCCA TGGCTCCACTGGCACCCCC 2530 GGGGTGCCAGTGGAGCCAGCTGGCTCCACTGGCACCCC 2531 GGGTGCCAGTGGAGCCAGC GCTGGCTCCACTGGCACCC 2532GGTGCCAGTGGAGCCAGCG CGCTGGCTCCACTGGCACC 2533 GTGCCAGTGGAGCCAGCGATCGCTGGCTCCACTGGCAC 2534 TGCCAGTGGAGCCAGCGAA TTCGCTGGCTCCACTGGCA 2535GCCAGTGGAGCCAGCGAAC GTTCGCTGGCTCCACTGGC 2536 CCAGTGGAGCCAGCGAACCGGTTCGCTGGCTCCACTGG 2537 CAGTGGAGCCAGCGAACCC GGGTTCGCTGGCTCCACTG 2538AGTGGAGCCAGCGAACCCA TGGGTTCGCTGGCTCCACT 2539 GTGGAGCCAGCGAACCCAGCTGGGTTCGCTGGCTCCAC 2540 TGGAGCCAGCGAACCCAGC GCTGGGTTCGCTGGCTCCA 2541GGAGCCAGCGAACCCAGCG CGCTGGGTTCGCTGGCTCC 2542 GAGCCAGCGAACCCAGCGATCGCTGGGTTCGCTGGCTC 2543 AGCCAGCGAACCCAGCGAG CTCGCTGGGTTCGCTGGCT 2544GCCAGCGAACCCAGCGAGG CCTCGCTGGGTTCGCTGGC 2545 CCAGCGAACCCAGCGAGGATCCTCGCTGGGTTCGCTGG 2546 CAGCGAACCCAGCGAGGAA TTCCTCGCTGGGTTCGCTG 2547AGCGAACCCAGCGAGGAAG CTTCCTCGCTGGGTTCGCT 2548 GCGAACCCAGCGAGGAAGTACTTCCTCGCTGGGTTCGC 2549 CGAACCCAGCGAGGAAGTG CACTTCCTCGCTGGGTTCG 2550GAACCCAGCGAGGAAGTGA TCACTTCCTCGCTGGGTTC 2551 AACCCAGCGAGGAAGTGAATTCACTTCCTCGCTGGGTT 2552 ACCCAGCGAGGAAGTGAAC GTTCACTTCCTCGCTGGGT 2553CCCAGCGAGGAAGTGAACA TGTTCACTTCCTCGCTGGG 2554 CCAGCGAGGAAGTGAACAATTGTTCACTTCCTCGCTGG 2555 CAGCGAGGAAGTGAACAAG CTTGTTCACTTCCTCGCTG 2556AGCGAGGAAGTGAACAAGG CCTTGTTCACTTCCTCGCT 2557 GCGAGGAAGTGAACAAGGCGCCTTGTTCACTTCCTCGC 2558 CGAGGAAGTGAACAAGGCC GGCCTTGTTCACTTCCTCG 2559GAGGAAGTGAACAAGGCCT AGGCCTTGTTCACTTCCTC 2560 AGGAAGTGAACAAGGCCTCGAGGCCTTGTTCACTTCCT 2561 GGAAGTGAACAAGGCCTCT AGAGGCCTTGTTCACTTCC 2562GAAGTGAACAAGGCCTCTG CAGAGGCCTTGTTCACTTC 2563 AAGTGAACAAGGCCTCTGGCCAGAGGCCTTGTTCACTT 2564 AGTGAACAAGGCCTCTGGC GCCAGAGGCCTTGTTCACT 2565GTGAACAAGGCCTCTGGCC GGCCAGAGGCCTTGTTCAC 2566 TGAACAAGGCCTCTGGCCCGGGCCAGAGGCCTTGTTCA 2567 GAACAAGGCCTCTGGCCCC GGGGCCAGAGGCCTTGTTC 2568AACAAGGCCTCTGGCCCCA TGGGGCCAGAGGCCTTGTT 2569 ACAAGGCCTCTGGCCCCAGCTGGGGCCAGAGGCCTTGT 2570 CAAGGCCTCTGGCCCCAGG CCTGGGGCCAGAGGCCTTG 2571AAGGCCTCTGGCCCCAGGG CCCTGGGGCCAGAGGCCTT 2572 AGGCCTCTGGCCCCAGGGCGCCCTGGGGCCAGAGGCCT 2573 GGCCTCTGGCCCCAGGGCC GGCCCTGGGGCCAGAGGCC 2574GCCTCTGGCCCCAGGGCCT AGGCCCTGGGGCCAGAGGC 2575 CCTCTGGCCCCAGGGCCTGCAGGCCCTGGGGCCAGAGG 2576 CTCTGGCCCCAGGGCCTGT ACAGGCCCTGGGGCCAGAG 2577TCTGGCCCCAGGGCCTGTC GACAGGCCCTGGGGCCAGA 2578 CTGGCCCCAGGGCCTGTCCGGACAGGCCCTGGGGCCAG 2579 TGGCCCCAGGGCCTGTCCC GGGACAGGCCCTGGGGCCA 2580GGCCCCAGGGCCTGTCCCC GGGGACAGGCCCTGGGGCC 2581 GCCCCAGGGCCTGTCCCCCGGGGGACAGGCCCTGGGGC 2582 CCCCAGGGCCTGTCCCCCC GGGGGGACAGGCCCTGGGG 2583CCCAGGGCCTGTCCCCCCA TGGGGGGACAGGCCCTGGG 2584 CCAGGGCCTGTCCCCCCAGCTGGGGGGACAGGCCCTGG 2585 CAGGGCCTGTCCCCCCAGC GCTGGGGGGACAGGCCCTG 2586AGGGCCTGTCGCCCCAGCC GGCTGGGGGGACAGGCCCT 2587 GGGCCTGTCCGCCCAGCCATGGCTGGGGGGACAGGCCC 2588 GGCCTGTCCCCCCAGCCAC GTGGCTGGGGGGACAGGCC 2589GCCTGTCCCCCCAGCCACC GGTGGCTGGGGGGACAGGC 2590 CCTGTCCCCCCAGCCACCATGGTGGCTGGGGGGACAGG 2591 CTGTCCCCCCAGCGACCAC GTGGTGGCTGGGGGGACAG 2592TGTCCCCCCAGCCACCACA TGTGGTGGCTGGGGGGACA 2593 GTCCCCCCAGCCACCACACGTGTGGTGGCTGGGGGGAC 2594 TCCCCCCAGCCACCACACC GGTGTGGTGGCTGGGGGGA 2595CCCCCCAGCCACCACACCA TGGTGTGGTGGCTGGGGGG 2596 CCCCCAGCCACCACACCAATTGGTGTGGTGGCTGGGGG 2597 CCCCAGCCACCACACCAAG CTTGGTGTGGTGGCTGGGG 2598CCCAGCCACCACACCAAGC GCTTGGTGTGGTGGCTGGG 2599 CCAGCCACCACACCAAGCTAGCTTGGTGTGGTGGCTGG 2600 CAGCCACCACACCAAGCTG CAGCTTGGTGTGGTGGCTG 2601AGCCACCACACCAAGCTGA TCAGCTTGGTGTGGTGGCT 2602 GCCACCACACCAAGCTGAATTCAGCTTGGTGTGGTGGC 2603 CCACCACACCAAGCTGAAG CTTCAGCTTGGTGTGGTGG 2604CACCACACCAAGCTGAAGA TCTTCAGCTTGGTGTGGTG 2605 ACCACACCAAGCTGAAGAATTCTTCAGCTTGGTGTGGT 2606 CCACACCAAGCTGAAGAAG CTTCTTCAGCTTGGTGTGG 2607CACACCAAGCTGAAGAAGA TCTTCTTCAGCTTGGTGTG 2608 ACACCAAGCTGAAGAAGACGTCTTCTTCAGCTTGGTGT 2609 CACCAAGCTGAAGAAGACA TGTCTTCTTCAGCTTGGTG 2610ACCAAGCTGAAGAAGACAT ATGTCTTCTTCAGCTTGGT 2611 CCAAGCTGAAGAAGACATGCATGTCTTCTTCAGCTTGG 2612 CAAGCTGAAGAAGACATGG CCATGTCTTCTTCAGCTTG 2613AAGCTGAAGAAGACATGGC GCCATGTCTTCTTCAGCTT 2614 AGCTGAAGAAGACATGGCTAGCCATGTCTTCTTCAGCT 2615 GCTGAAGAAGACATGGCTC GAGCCATGTCTTCTTCAGC 2616CTGAAGAAGACATGGCTCA TGAGCCATGTCTTCTTCAG 2617 TGAAGAAGACATGGCTCACGTGAGCCATGTCTTCTTCA 2618 GAAGAAGACATGGCTCACA TGTGAGCCATGTCTTCTTC 2619AAGAAGACATGGCTCACAC GTGTGAGCCATGTCTTCTT 2620 AGAAGACATGGCTCACACGCGTGTGAGCCATGTCTTCT 2621 GAAGACATGGCTCACACGG CCGTGTGAGCCATGTCTTC 2622AAGACATGGCTCACACGGC GCCGTGTGAGCCATGTCTT 2623 AGACATGGCTCACACGGCATGCCGTGTGAGCCATGTCT 2624 GACATGGCTCACACGGCAC GTGCCGTGTGAGCCATGTC 2625ACATGGCTCACACGGCACT AGTGCCGTGTGAGCCATGT 2626 CATGGCTCACACGGCACTCGAGTGCCGTGTGAGCCATG 2627 ATGGCTCACACGGCACTCG CGAGTGCCGTGTGAGCCAT 2628TGGCTCACACGGCACTCGG CCGAGTGCCGTGTGAGCCA 2629 GGCTCACACGGCACTCGGATCCGAGTGCCGTGTGAGCC 2630 GCTCACACGGCACTCGGAG CTCCGAGTGCCGTGTGAGC 2631CTCACACGGCACTCGGAGC GCTCCGAGTGCCGTGTGAG 2632 TCACACGGCACTCGGAGCATGCTCCGAGTGCCGTGTGA 2633 CACACGGCACTCGGAGCAG CTGCTCCGAGTGCCGTGTG 2634ACACGGCACTCGGAGCAGT ACTGCTCCGAGTGCCGTGT 2635 CACGGCACTCGGAGCAGTTAACTGCTCCGAGTGCCGTG 2636 ACGGCACTCGGAGCAGTTT AAACTGCTCCGAGTGCCGT 2637CGGCACTCGGAGCAGTTTG CAAACTGCTCCGAGTGCCG 2638 GGCACTCGGAGCAGTTTGATCAAACTGCTCCGAGTGCC 2639 GCACTCGGAGCAGTTTGAA TTCAAACTGCTCCGAGTGC 2640CACTCGGAGCAGTTTGAAT ATTCAAACTGCTCCGAGTG 2641 ACTCGGAGCAGTTTGAATGCATTCAAACTGCTCCGAGT 2642 CTCGGAGCAGTTTGAATGT ACATTCAAACTGCTCCGAG 2643TCGGAGCAGTTTGAATGTC GACATTCAAACTGCTCCGA 2644 CGGAGCAGTTTGAATGTCCGGACATTCAAACTGCTCCG 2645 GGAGCAGTTTGAATGTCCA TGGACATTCAAACTGCTCC 2646GAGCAGTTTGAATGTCCAC GTGGACATTCAAACTGCTC 2647 AGCAGTTTGAATGTCCACGCGTGGACATTCAAACTGCT 2648 GCAGTTTGAATGTCCACGC GCGTGGACATTCAAACTGC 2649CAGTTTGAATGTCCACGCG CGCGTGGACATTCAAACTG 2650 AGTTTGAATGTCCACGCGGCCGCGTGGACATTCAAACT 2651 GTTTGAATGTCCACGCGGC GCCGCGTGGACATTCAAAC 2652TTTGAATGTCCACGCGGCT AGCCGCGTGGACATTCAAA 2653 TTGAATGTCCACGCGGCTGCAGCCGCGTGGACATTCAA 2654 TGAATGTCCACGCGGCTGC GCAGCCGCGTGGACATTCA 2655GAATGTCCACGCGGCTGCC GGCAGCCGCGTGGACATTC 2656 AATGTCCACGCGGCTGCCCGGGCAGCCGCGTGGACATT 2657 ATGTCCACGCGGCTGCCCT AGGGCAGCCGCGTGGACAT 2658TGTCCACGCGGCTGCCCTG CAGGGCAGCCGCGTGGACA 2659 GTCCACGCGGCTGCCCTGATCAGGGCAGCCGCGTGGAC 2660 TCCACGCGGCTGCCCTGAG CTCAGGGCAGCCGCGTGGA 2661CCACGCGGCTGCCCTGAGG CCTCAGGGCAGCCGCGTGG 2662 CACGCGGCTGCCCTGAGGTACCTCAGGGCAGCCGCGTG 2663 ACGCGGCTGCCCTGAGGTC GACCTCAGGGCAGCCGCGT 2664CGCGGCTGCCCTGAGGTCG CGACCTCAGGGCAGCCGCG 2665 GCGGCTGCCCTGAGGTCGATCGACCTCAGGGCAGCCGC 2666 CGGCTGCCCTGAGGTCGAG CTCGACCTCAGGGCAGCCG 2667GGCTGCCCTGAGGTCGAGG CCTCGACCTCAGGGCAGCC 2668 GCTGCCCTGAGGTCGAGGATCCTCGACCTCAGGGCAGC 2669 CTGCCCTGAGGTCGAGGAG CTCCTCGACCTCAGGGCAG 2670TGCCCTGAGGTCGAGGAGA TCTCCTCGACCTCAGGGCA 2671 GCCCTGAGGTCGAGGAGAGCTCTCCTCGACCTCAGGGC 2672 CCCTGAGGTCGAGGAGAGG CCTCTCCTCGACCTCAGGG 2673CCTGAGGTCGAGGAGAGGC GCCTCTCCTCGACCTCAGG 2674 CTGAGGTCGAGGAGAGGCCGGCCTCTCCTCGACCTCAG 2675 TGAGGTCGAGGAGAGGCCG CGGCCTCTCCTCGACCTCA 2676GAGGTCGAGGAGAGGCCGG CCGGCCTCTCCTCGACCTC 2677 AGGTCGAGGAGAGGCCGGTACCGGCCTCTCCTCGACCT 2678 GGTCGAGGAGAGGCCGGTT AACCGGCCTCTCCTCGACC 2679GTCGAGGAGAGGCCGGTTG CAACCGGCCTCTCCTCGAC 2680 TCGAGGAGAGGCCGGTTGCGCAACCGGCCTCTCCTCGA 2681 CGAGGAGAGGCCGGTTGCT AGCAACCGGCCTCTCCTCG 2682GAGGAGAGGCCGGTTGCTC GAGCAACCGGCCTCTCCTC 2683 AGGAGAGGCCGGTTGCTCGCGAGCAACCGGCCTCTCCT 2684 GGAGAGGCCGGTTGCTCGG CCGAGCAACCGGCCTCTCC 2685GAGAGGCCGGTTGCTCGGC GCCGAGCAACCGGCCTCTC 2686 AGAGGCCGGTTGCTCGGCTAGCCGAGCAACCGGCCTCT 2687 GAGGCCGGTTGCTCGGCTC GAGCCGAGCAACCGGCCTC 2688AGGCCGGTTGCTCGGCTCC GGAGCCGAGCAACCGGCCT 2689 GGCCGGTTGCTCGGCTCCGCGGAGCCGAGCAACCGGCC 2690 GCCGGTTGCTCGGCTCCGG CCGGAGCCGAGCAACCGGC 2691CCGGTTGCTCGGCTCCGGG CCCGGAGCCGAGCAACCGG 2692 CGGTTGCTCGGCTCCGGGCGCCCGGAGCCGAGCAACCG 2693 GGTTGCTCGGCTCCGGGCC GGCCCGGAGCCGAGCAACC 2694GTTGCTCGGCTCCGGGCCC GGGCCCGGAGCCGAGCAAC 2695 TTGCTCGGCTCCGGGCCCTAGGGCCCGGAGCCGAGCAA 2696 TGCTCGGCTCCGGGCCCTC GAGGGCCCGGAGCCGAGCA 2697GCTCGGCTCCGGGCCCTCA TGAGGGCCCGGAGCCGAGC 2698 CTCGGCTCCGGGCCCTCAATTGAGGGCCCGGAGCCGAG 2699 TCGGCTCCGGGCCCTCAAA TTTGAGGGCCCGGAGCCGA 2700CGGCTCCGGGCCCTCAAAA TTTTGAGGGCCCGGAGCCG 2701 GGCTCCGGGCCCTCAAAAGCTTTTGAGGGCCCGGAGCC 2702 GCTCCGGGCCCTCAAAAGG CCTTTTGAGGGCCCGGAGC 2703CTCCGGGCCCTCAAAAGGG CCCTTTTGAGGGCCCGGAG 2704 TCCGGGCCCTCAAAAGGGCGCCCTTTTGAGGGCCCGGA 2705 CCGGGCCCTCAAAAGGGCA TGCCCTTTTGAGGGCCCGG 2706CGGGCCCTCAAAAGGGCAG CTGCCCTTTTGAGGGCCCG 2707 GGGCCCTCAAAAGGGCAGGCCTGCCCTTTTGAGGGCCC 2708 GGCCCTCAAAAGGGCAGGC GCCTGCCCTTTTGAGGGCC 2709GCCCTCAAAAGGGCAGGCA TGCCTGCCCTTTTGAGGGC 2710 CCCTCAAAAGGGCAGGCAGCTGCCTGCCCTTTTGAGGG 2711 CCTCAAAAGGGCAGGCAGC GCTGCCTGCCCTTTTGAGG 2712CTCAAAAGGGCAGGCAGCC GGCTGCCTGCCCTTTTGAG 2713 TCAAAAGGGCAGGCAGCCCGGGCTGCCTGCCCTTTTGA 2714 CAAAAGGGCAGGCAGCCCC GGGGCTGCCTGCCCTTTTG 2715AAAAGGGCAGGCAGCCCCG CGGGGCTGCCTGCCCTTTT 2716 AAAGGGCAGGCAGCCCCGATCGGGGCTGCCTGCCCTTT 2717 AAGGGCAGGCAGCCCCGAG CTCGGGGCTGCCTGCCCTT 2718AGGGCAGGCAGCCCCGAGG CCTCGGGGCTGCCTGCCCT 2719 GGGCAGGCAGCCCCGAGGTACCTCGGGGCTGCCTGCCC 2720 GGCAGGCAGCCCCGAGGTC GACCTCGGGGCTGCCTGCC 2721GCAGGCAGCCCCGAGGTCC GGACCTCGGGGCTGCCTGC 2722 CAGGCAGCCCCGAGGTCCATGGACCTCGGGGCTGCCTG 2723 AGGCAGCCCCGAGGTCCAG CTGGACCTCGGGGCTGCCT 2724GGCAGCCCCGAGGTCCAGG CCTGGACCTCGGGGCTGCC 2725 GCAGCCCCGAGGTCCAGGGCCCTGGACCTCGGGGCTGC 2726 CAGCCCCGAGGTCCAGGGA TCCCTGGACCTCGGGGCTG 2727AGCCCCGAGGTCCAGGGAG CTCCCTGGACCTCGGGGCT 2728 GCCCCGAGGTCCAGGGAGCGCTCCCTGGACCTCGGGGC 2729 CCCCGAGGTCCAGGGAGCA TGCTCCCTGGACCTCGGGG 2730CCCGAGGTCCAGGGAGCAA TTGCTCCCTGGACCTCGGG 2731 CCGAGGTCCAGGGAGCAATATTGCTCCCTGGACCTCGG 2732 CGAGGTCCAGGGAGCAATG CATTGCTCCCTGGACCTCG 2733GAGGTCCAGGGAGCAATGG CCATTGCTCCCTGGACCTC 2734 AGGTCCAGGGAGCAATGGGCCCATTGCTCCCTGGACCT 2735 GGTCCAGGGAGCAATGGGC GCCCATTGCTCCCTGGACC 2736GTCCAGGGAGCAATGGGCA TGCCCATTGCTCCCTGGAC 2737 TCCAGGGAGCAATGGGCAGCTGCCCATTGCTCCCTGGA 2738 CCAGGGAGCAATGGGCAGT ACTGCCCATTGCTCCCTGG 2739CAGGGAGCAATGGGCAGTC GACTGCCCATTGCTCCCTG 2740 AGGGAGCAATGGGCAGTCCGGACTGCCCATTGCTCCCT 2741 GGGAGCAATGGGCAGTCCA TGGACTGCCCATTGCTCCC 2742GGAGCAATGGGCAGTCCAG CTGGACTGCCCATTGCTCC 2743 GAGCAATGGGCAGTCCAGCGCTGGACTGCCCATTGCTC 2744 AGCAATGGGCAGTCCAGCC GGCTGGACTGCCCATTGCT 2745GCAATGGGCAGTCCAGCCC GGGCTGGACTGCCCATTGC 2746 CAATGGGCAGTCCAGCCCCGGGGCTGGACTGCCCATTG 2747 AATGGGCAGTCCAGCCCCC GGGGGCTGGACTGCCCATT 2748ATGGGCAGTCCAGCCCCCA TGGGGGCTGGACTGCCCAT 2749 TGGGCAGTCCAGCCCCCAATTGGGGGCTGGACTGCCCA 2750 GGGCAGTCCAGCCCCCAAG CTTGGGGGCTGGACTGCCC 2751GGCAGTCCAGCCCCCAAGC GCTTGGGGGCTGGACTGCC 2752 GCAGTCCAGCCCCCAAGCGCGCTTGGGGGCTGGACTGC 2753 CAGTCCAGCCCCCAAGCGG CCGCTTGGGGGCTGGACTG 2754AGTCCAGCCCCCAAGCGGC GCCGCTTGGGGGCTGGACT 2755 GTCCAGCCCCCAAGCGGCCGGCCGCTTGGGGGCTGGAC 2756 TCCAGCCCCCAAGCGGCCA TGGCCGCTTGGGGGCTGGA 2757CCAGCCCCCAAGCGGCCAC GTGGCCGCTTGGGGGCTGG 2758 CAGCCCCCAAGCGGCCACCGGTGGCCGCTTGGGGGCTG 2759 AGCCCCCAAGCGGCCACCG CGGTGGCCGCTTGGGGGCT 2760GCCCCCAAGCGGCCACCGG CCGGTGGCCGCTTGGGGGC 2761 CCCCCAAGCGGCCACCGGATCCGGTGGCCGCTTGGGGG 2762 CCCCAAGCGGCCACCGGAC GTCCGGTGGCCGCTTGGGG 2763CCCAAGCGGCCACCGGACC GGTCCGGTGGCCGCTTGGG 2764 CCAAGCGGCCACCGGACCCGGGTCCGGTGGCCGCTTGG 2765 CAAGCGGCCACCGGACCCT AGGGTCCGGTGGCCGCTTG 2766AAGCGGCCACCGGACCCTT AAGGGTCCGGTGGCCGCTT 2767 AGCGGCCACCGGACCCTTTAAAGGGTCCGGTGGCCGCT 2768 GCGGCCACCGGACCCTTTT AAAAGGGTCCGGTGGCCGC 2769CGGCCACCGGACCCTTTTC GAAAAGGGTCCGGTGGCCG 2770 GGCCACCGGACCCTTTTCCGGAAAAGGGTCCGGTGGCC 2771 GCCACCGGACCCTTTTCCA TGGAAAAGGGTCCGGTGGC 2772CCACCGGACCCTTTTCCAG CTGGAAAAGGGTCCGGTGG 2773 CACCGGACCCTTTTCCAGGCCTGGAAAAGGGTCCGGTG 2774 ACCGGACCCTTTTCCAGGC GCCTGGAAAAGGGTCCGGT 2775CCGGACCCTTTTCCAGGCA TGCCTGGAAAAGGGTCCGG 2776 CGGACCCTTTTCCAGGCACGTGCCTGGAAAAGGGTCCG 2777 GGACCCTTTTCCAGGCACT AGTGCCTGGAAAAGGGTCC 2778GACCCTTTTCCAGGCACTG CAGTGCCTGGAAAAGGGTC 2779 ACCCTTTTCCAGGCACTGCGCAGTGCCTGGAAAAGGGT 2780 CCCTTTTCCAGGCACTGCA TGCAGTGCCTGGAAAAGGG 2781CCTTTTCCAGGCACTGCAG CTGCAGTGCCTGGAAAAGG 2782 CTTTTCCAGGCACTGCAGATCTGCAGTGCCTGGAAAAG 2783 TTTTCCAGGCACTGCAGAA TTCTGCAGTGCCTGGAAAA 2784TTTCCAGGCACTGCAGAAC GTTCTGCAGTGCCTGGAAA 2785 TTCCAGGCACTGCAGAACATGTTCTGCAGTGCCTGGAA 2786 TCCAGGCACTGCAGAACAG CTGTTCTGCAGTGCCTGGA 2787CCAGGCACTGCAGAACAGG CCTGTTCTGCAGTGCCTGG 2788 CAGGCACTGCAGAACAGGGCCCTGTTCTGCAGTGCCTG 2789 AGGCACTGCAGAACAGGGG CCCCTGTTCTGCAGTGCCT 2790GGCACTGCAGAACAGGGGG CCCCCTGTTCTGCAGTGCC 2791 GCACTGCAGAACAGGGGGCGCCCCCTGTTCTGCAGTGC 2792 CACTGCAGAACAGGGGGCT AGCCCCCTGTTCTGCAGTG 2793ACTGCAGAACAGGGGGCTG CAGCCCCCTGTTCTGCAGT 2794 CTGCAGAACAGGGGGCTGGCCAGCCCCCTGTTCTGCAG 2795 TGCAGAACAGGGGGCTGGG CCCAGCCCCCTGTTCTGCA 2796GCAGAACAGGGGGCTGGGG CCCCAGCCCCCTGTTCTGC 2797 CAGAACAGGGGGCTGGGGGCCCCCAGCCCCCTGTTCTG 2798 AGAACAGGGGGCTGGGGGT ACCCCCAGCCCCCTGTTCT 2799GAACAGGGGGCTGGGGGTT AACCCCCAGCCCCCTGTTC 2800 AACAGGGGGCTGGGGGTTGCAACCCCCAGCCCCCTGTT 2801 ACAGGGGGCTGGGGGTTGG CCAACCCCCAGCCCCCTGT 2802CAGGGGGCTGGGGGTTGGC GCCAACCCCCAGCCCCCTG 2803 AGGGGGCTGGGGGTTGGCATGCCAACCCCCAGCCCCCT 2804 GGGGGCTGGGGGTTGGCAG CTGCCAACCCCCAGCCCCC 2805GGGGCTGGGGGTTGGCAGG CCTGCCAACCCCCAGCCCC 2806 GGGCTGGGGGTTGGCAGGATCCTGCCAACCCCCAGCCC 2807 GGCTGGGGGTTGGCAGGAG CTCCTGCCAACCCCCAGCC 2808GCTGGGGGTTGGCAGGAGG CCTCCTGCCAACCCCCAGC 2809 CTGGGGGTTGGCAGGAGGTACCTCCTGCCAACCCCCAG 2810 TGGGGGTTGGCAGGAGGTG CACCTCCTGCCAACCCCCA 2811GGGGGTTGGCAGGAGGTGC GCACCTCCTGCCAACCCCC 2812 GGGGTTGGCAGGAGGTGCGCGCACCTCCTGCCAACCCC 2813 GGGTTGGCAGGAGGTGCGG CCGCACCTCCTGCCAACCC 2814GGTTGGCAGGAGGTGCGGG CCCGCACCTCCTGCCAACC 2815 GTTGGCAGGAGGTGCGGGATCCCGCACCTCCTGCCAAC 2816 TTGGCAGGAGGTGCGGGAC GTCCCGCACCTCCTGCCAA 2817TGGCAGGAGGTGCGGGACA TGTCCCGCACCTCCTGCCA 2818 GGCAGGAGGTGCGGGACACGTGTCCCGCACCTCCTGCC 2819 GCAGGAGGTGCGGGACACA TGTGTCCCGCACCTCCTGC 2820CAGGAGGTGCGGGACACAT ATGTGTCCCGCACCTCCTG 2821 AGGAGGTGCGGGACACATCGATGTGTCCCGCACCTCCT 2822 GGAGGTGCGGGACACATCG CGATGTGTCCCGCACCTCC 2823GAGGTGCGGGACACATCGA TCGATGTGTCCCGCACCTC 2824 AGGTGCGGGACACATCGATATCGATGTGTCCCGCACCT 2825 GGTGCGGGACACATCGATA TATCGATGTGTCCCGCACC 2826GTGCGGGACACATCGATAG CTATCGATGTGTCCCGCAC 2827 TGCGGGACACATCGATAGGCCTATCGATGTGTCCCGCA 2828 GCGGGACACATCGATAGGG CCCTATCGATGTGTCCCGC 2829CGGGACACATCGATAGGGA TCCCTATCGATGTGTCCCG 2830 GGGACACATCGATAGGGAATTCCCTATCGATGTGTCCC 2831 GGACACATCGATAGGGAAC GTTCCCTATCGATGTGTCC 2832GACACATCGATAGGGAACA TGTTCCCTATCGATGTGTC 2833 ACACATCGATAGGGAACAATTGTTCCCTATCGATGTGT 2834 CACATCGATAGGGAACAAG CTTGTTCCCTATCGATGTG 2835ACATCGATAGGGAACAAGG CCTTGTTCCCTATCGATGT 2836 CATCGATAGGGAACAAGGATCCTTGTTCCCTATCGATG 2837 ATCGATAGGGAACAAGGAT ATCCTTGTTCCCTATCGAT 2838TCGATAGGGAACAAGGATG CATCCTTGTTCCCTATCGA 2839 CGATAGGGAACAAGGATGTACATCCTTGTTCCCTATCG 2840 GATAGGGAACAAGGATGTG CACATCCTTGTTCCCTATC 2841ATAGGGAACAAGGATGTGG CCACATCCTTGTTCCCTAT 2842 TAGGGAACAAGGATGTGGATCCACATCCTTGTTCCCTA 2843 AGGGAACAAGGATGTGGAC GTCCACATCCTTGTTCCCT 2844GGGAACAAGGATGTGGACT AGTCCACATCCTTGTTCCC 2845 GGAACAAGGATGTGGACTCGAGTCCACATCCTTGTTCC 2846 GAACAAGGATGTGGACTCG CGAGTCCACATCCTTGTTC 2847AACAAGGATGTGGACTCGG CCGAGTCCACATCCTTGTT 2848 ACAAGGATGTGGACTCGGGCCCGAGTCCACATCCTTGT 2849 CAAGGATGTGGACTCGGGA TCCCGAGTCCACATCCTTG 2850AAGGATGTGGACTCGGGAC GTCCCGAGTCCACATCCTT 2851 AGGATGTGGACTCGGGACATGTCCCGAGTCCACATCCT 2852 GGATGTGGACTCGGGACAG CTGTCCCGAGTCCACATCC 2853GATGTGGACTCGGGACAGC GCTGTCCCGAGTCCACATC 2854 ATGTGGACTCGGGACAGCATGCTGTCCCGAGTCCACAT 2855 TGTGGACTCGGGACAGCAT ATGCTGTCCCGAGTCCACA 2856GTGGACTCGGGACAGCATG CATGCTGTCCCGAGTCCAC 2857 TGGACTCGGGACAGCATGATCATGCTGTCCCGAGTCCA 2858 GGACTCGGGACAGCATGAT ATCATGCTGTCCCGAGTCC 2859GACTCGGGACAGCATGATG CATCATGCTGTCCCGAGTC 2860 ACTCGGGACAGCATGATGATCATCATGCTGTCCCGAGT 2861 CTCGGGACAGCATGATGAG CTCATCATGCTGTCCCGAG 2862TCGGGACAGCATGATGAGC GCTCATCATGCTGTCCCGA 2863 CGGGACAGCATGATGAGCATGCTCATCATGCTGTCCCG 2864 GGGACAGCATGATGAGCAG CTGCTCATCATGCTGTCCC 2865GGACAGCATGATGAGCAGA TCTGCTCATCATGCTGTCC 2866 GACAGCATGATGAGCAGAATTCTGCTCATCATGCTGTC 2867 ACAGCATGATGAGCAGAAA TTTCTGCTCATCATGCTGT 2868CAGCATGATGAGCAGAAAG CTTTCTGCTCATCATGCTG 2869 AGCATGATGAGCAGAAAGGCCTTTCTGCTCATCATGCT 2870 GCATGATGAGCAGAAAGGA TCCTTTCTGCTCATCATGC 2871CATGATGAGCAGAAAGGAC GTCCTTTCTGCTCATCATG 2872 ATGATGAGCAGAAAGGACCGGTCCTTTCTGCTCATCAT 2873 TGATGAGCAGAAAGGACCC GGGTCCTTTCTGCTCATCA 2874GATGAGCAGAAAGGACCCC GGGGTCCTTTCTGCTCATC 2875 ATGAGCAGAAAGGACCCCATGGGGTCCTTTCTGCTCAT 2876 TGAGCAGAAAGGACCCCAA TTGGGGTCCTTTCTGCTCA 2877GAGCAGAAAGGACCCCAAG CTTGGGGTCCTTTCTGCTC 2878 AGCAGAAAGGACCCCAAGATCTTGGGGTCCTTTCTGCT 2879 GCAGAAAGGACCCCAAGAT ATCTTGGGGTCCTTTCTGC 2880CAGAAAGGACCCCAAGATG CATCTTGGGGTCCTTTCTG 2881 AGAAAGGACCCCAAGATGGCCATCTTGGGGTCCTTTCT 2882 GAAAGGACCCCAAGATGGC GCCATCTTGGGGTCCTTTC 2883AAAGGACCCCAAGATGGCC GGCCATCTTGGGGTCCTTT 2884 AAGGACCCCAAGATGGCCATGGCCATCTTGGGGTCCTT 2885 AGGACCCCAAGATGGCCAG CTGGCCATCTTGGGGTCCT 2886GGACCCCAAGATGGCCAGG CCTGGCCATCTTGGGGTCC 2887 GACCCCAAGATGGCCAGGCGCCTGGCCATCTTGGGGTC 2888 ACCCCAAGATGGCCAGGCC GGCCTGGCCATCTTGGGGT 2889CCCCAAGATGGCCAGGCCA TGGCCTGGCCATCTTGGGG 2890 CCCAAGATGGCCAGGCCAGCTGGCCTGGCCATCTTGGG 2891 CCAAGATGGCCAGGCCAGT ACTGGCCTGGCCATCTTGG 2892CAAGATGGCCAGGCCAGTC GACTGGCCTGGCCATCTTG 2893 AAGATGGCCAGGCCAGTCTAGACTGGCCTGGCCATCTT 2894 AGATGGCCAGGCCAGTCTC GAGACTGGCCTGGCCATCT 2895GATGGCCAGGCCAGTCTCC GGAGACTGGCCTGGCCATC 2896 ATGGCCAGGCCAGTCTCCATGGAGACTGGCCTGGCCAT 2897 TGGCCAGGCCAGTCTCCAG CTGGAGACTGGCCTGGCCA 2898GGCCAGGCCAGTCTCCAGG CCTGGAGACTGGCCTGGCC 2899 GCCAGGCCAGTCTCCAGGATCCTGGAGACTGGCCTGGC 2900 CCAGGCCAGTCTCCAGGAC GTCCTGGAGACTGGCCTGG 2901CAGGCCAGTCTCCAGGACC GGTCCTGGAGACTGGCCTG 2902 AGGCCAGTCTCCAGGACCCGGGTCCTGGAGACTGGCCT 2903 GGCCAGTCTCCAGGACCCG CGGGTCCTGGAGACTGGCC 2904GCCAGTCTCCAGGACCCGG CCGGGTCCTGGAGACTGGC 2905 CCAGTCTCCAGGACCCGGGCCCGGGTCCTGGAGACTGG 2906 CAGTCTCCAGGACCCGGGA TCCCGGGTCCTGGAGACTG 2907AGTCTCCAGGACCCGGGAC GTCCCGGGTCCTGGAGACT 2908 GTCTCCAGGACCCGGGACTAGTCCCGGGTCCTGGAGAC 2909 TCTCCAGGACCCGGGACTT AAGTCCCGGGTCCTGGAGA 2910CTCCAGGACCCGGGACTTC GAAGTCCCGGGTCCTGGAG 2911 TCCAGGACCCGGGACTTCATGAAGTCCCGGGTCCTGGA 2912 CCAGGACCCGGGACTTCAG CTGAAGTCCCGGGTCCTGG 2913CAGGACCCGGGACTTCAGG CCTGAAGTCCCGGGTCCTG 2914 AGGACCCGGGACTTCAGGATCCTGAAGTCCCGGGTCCT 2915 GGACCCGGGACTTCAGGAC GTCCTGAAGTCCCGGGTCC 2916GACCCGGGACTTCAGGACA TGTCCTGAAGTCCCGGGTC 2917 ACCCGGGACTTCAGGACATATGTCCTGAAGTCCCGGGT 2918 CCCGGGACTTCAGGACATA TATGTCCTGAAGTCCCGGG 2919CCGGGACTTCAGGACATAC GTATGTCCTGAAGTCCCGG 2920 CGGGACTTCAGGACATACCGGTATGTCCTGAAGTCCCG 2921 GGGACTTCAGGACATACCA TGGTATGTCCTGAAGTCCC 2922GGACTTCAGGACATACCAT ATGGTATGTCCTGAAGTCC 2923 GACTTCAGGACATACCATGCATGGTATGTCCTGAAGTC 2924 ACTTCAGGACATACCATGC GCATGGTATGTCCTGAAGT 2925CTTCAGGACATACCATGCC GGCATGGTATGTCCTGAAG 2926 TTCAGGACATACCATGCCTAGGCATGGTATGTCCTGAA 2927 TCAGGACATACCATGCCTG CAGGCATGGTATGTCCTGA 2928CAGGACATACCATGCCTGG CCAGGCATGGTATGTCCTG 2929 AGGACATACCATGCCTGGCGCCAGGCATGGTATGTCCT 2930 GGACATACCATGCCTGGCT AGCCAGGCATGGTATGTCC 2931GACATACCATGCCTGGCTC GAGCCAGGCATGGTATGTC 2932 ACATACCATGCCTGGCTCTAGAGCCAGGCATGGTATGT 2933 CATACCATGCCTGGCTCTC GAGAGCCAGGCATGGTATG 2934ATACCATGCCTGGCTCTCC GGAGAGCCAGGCATGGTAT 2935 TACCATGCCTGGCTCTCCCGGGAGAGCCAGGCATGGTA 2936 ACCATGCCTGGCTCTCCCT AGGGAGAGCCAGGCATGGT 2937CCATGCCTGGCTCTCCCTG CAGGGAGAGCCAGGCATGG 2938 CATGCCTGGCTCTCCCTGCGCAGGGAGAGCCAGGCATG 2939 ATGCCTGGCTCTCCCTGCA TGCAGGGAGAGCCAGGCAT 2940TGCCTGGCTCTCCCTGCAA TTGCAGGGAGAGCCAGGCA 2941 GCCTGGCTCTCCCTGCAAATTTGCAGGGAGAGCCAGGC 2942 CCTGGCTCTCCCTGCAAAA TTTTGCAGGGAGAGCCAGG 2943CTGGCTCTCCCTGCAAAAC GTTTTGCAGGGAGAGCCAG 2944 TGGCTCTCCCTGCAAAACTAGTTTTGCAGGGAGAGCCA 2945 GGCTCTCCCTGCAAAACTG CAGTTTTGCAGGGAGAGCC 2946GCTCTCCCTGCAAAACTGG CCAGTTTTGCAGGGAGAGC 2947 CTCTCCCTGCAAAACTGGCGCCAGTTTTGCAGGGAGAG 2948 TCTCCCTGCAAAACTGGCT AGCCAGTTTTGCAGGGAGA 2949CTCCCTGCAAAACTGGCTC GAGCCAGTTTTGCAGGGAG 2950 TCCCTGCAAAACTGGCTCATGAGCCAGTTTTGCAGGGA 2951 CCCTGCAAAACTGGCTCAA TTGAGCCAGTTTTGCAGGG 2952CCTGCAAAACTGGCTCAAT ATTGAGCCAGTTTTGCAGG 2953 CTGCAAAACTGGCTCAATGCATTGAGCCAGTTTTGCAG 2954 TGCAAAACTGGCTCAATGC GCATTGAGCCAGTTTTGCA 2955GCAAAACTGGCTCAATGCC GGCATTGAGCCAGTTTTGC 2956 CAAAACTGGCTCAATGCCATGGCATTGAGCCAGTTTTG 2957 AAAACTGGCTCAATGCCAA TTGGCATTGAGCCAGTTTT 2958AAACTGGCTCAATGCCAAA TTTGGCATTGAGCCAGTTT 2959 AACTGGCTCAATGCCAAAGCTTTGGCATTGAGCCAGTT 2960 ACTGGCTCAATGCCAAAGT ACTTTGGCATTGAGCCAGT 2961CTGGCTCAATGCCAAAGTT AACTTTGGCATTGAGCCAG 2962 TGGCTCAATGCCAAAGTTGCAACTTTGGCATTGAGCCA 2963 GGCTCAATGCCAAAGTTGT ACAACTTTGGCATTGAGCC 2964GCTCAATGCCAAAGTTGTG CACAACTTTGGCATTGAGC 2965 CTCAATGCCAAAGTTGTGCGCACAACTTTGGCATTGAG 2966 TCAATGCCAAAGTTGTGCC GGCACAACTTTGGCATTGA 2967CAATGCCAAAGTTGTGCCC GGGCACAACTTTGGCATTG 2968 AATGCCAAAGTTGTGCCCATGGGCACAACTTTGGCATT 2969 ATGCCAAAGTTGTGCCCAG CTGGGCACAACTTTGGCAT 2970TGCCAAAGTTGTGCCCAGG CCTGGGCACAACTTTGGCA 2971 GCCAAAGTTGTGCCCAGGCGCCTGGGCACAACTTTGGC 2972 CCAAAGTTGTGCCCAGGCA TGCCTGGGCACAACTTTGG 2973CAAAGTTGTGCCCAGGCAG CTGCCTGGGCACAACTTTG 2974 AAAGTTGTGCCCAGGCAGCGCTGCCTGGGCACAACTTT 2975 AAGTTGTGCCCAGGCAGCT AGCTGCCTGGGCACAACTT 2976AGTTGTGCCCAGGCAGCTG CAGCTGCCTGGGCACAACT 2977 GTTGTGCCCAGGCAGCTGGCCAGCTGCCTGGGCACAAC 2978 TTGTGCCCAGGCAGCTGGA TCCAGCTGCCTGGGCACAA 2979TGTGCCCAGGCAGCTGGAG CTCCAGCTGCCTGGGCACA 2980 GTGCCCAGGCAGCTGGAGATCTCCAGCTGCCTGGGCAC 2981 TGCCCAGGCAGCTGGAGAG CTCTCCAGCTGCCTGGGCA 2982GCCCAGGCAGCTGGAGAGG CCTCTCCAGCTGCCTGGGC 2983 CCCAGGCAGCTGGAGAGGGCCCTCTCCAGCTGCCTGGG 2984 CCAGGCAGCTGGAGAGGGA TCCCTCTCCAGCTGCCTGG 2985CAGGCAGCTGGAGAGGGAG CTCCCTCTCCAGCTGCCTG 2986 AGGCAGCTGGAGAGGGAGGCCTCCCTCTCCAGCTGCCT 2987 GGCAGCTGGAGAGGGAGGA TCCTCCCTCTCCAGCTGCC 2988GCAGCTGGAGAGGGAGGAG CTCCTCCCTCTCCAGCTGC 2989 CAGCTGGAGAGGGAGGAGGCCTCCTCCCTCTCCAGCTG 2990 AGCTGGAGAGGGAGGAGGG CCCTCCTCCCTCTCCAGCT 2991GCTGGAGAGGGAGGAGGGC GCCCTCCTCCCTCTCCAGC 2992 CTGGAGAGGGAGGAGGGCATGCCCTCCTCCCTCTCCAG 2993 TGGAGAGGGAGGAGGGCAC GTGCCCTCCTCCCTCTCCA 2994GGAGAGGGAGGAGGGCACG CGTGCCCTCCTCCCTCTCC 2995 GAGAGGGAGGAGGGCACGCGCGTGCCCTCCTCCCTCTC 2996 AGAGGGAGGAGGGCACGCC GGCGTGCCCTCCTCCCTCT 2997GAGGGAGGAGGGCACGCCT AGGCGTGCCCTCCTCCCTC 2998 AGGGAGGAGGGCACGCCTGCAGGCGTGCCCTCCTCCCT 2999 GGGAGGAGGGCACGCCTGC GCAGGCGTGCCCTCCTCCC 3000GGAGGAGGGCACGCCTGCC GGCAGGCGTGCCCTCCTCC 3001 GAGGAGGGCACGCCTGCCATGGCAGGCGTGCCCTCCTC 3002 AGGAGGGCACGCCTGCCAC GTGGCAGGCGTGCCCTCCT 3003GGAGGGCACGCCTGCCACT AGTGGCAGGCGTGCCCTCC 3004 GAGGGCACGCCTGCCACTCGAGTGGCAGGCGTGCCCTC 3005 AGGGCACGCCTGCCACTCT AGAGTGGCAGGCGTGCCCT 3006GGGCACGCCTGCCACTCTC GAGAGTGGCAGGCGTGCCC 3007 GGCACGCCTGCCACTCTCATGAGAGTGGCAGGCGTGCC 3008 GCACGCCTGCCACTCTCAG CTGAGAGTGGCAGGCGTGC 3009CACGCCTGCCACTCTCAGC GCTGAGAGTGGCAGGCGTG 3010 ACGCCTGCCACTCTCAGCATGCTGAGAGTGGCAGGCGT 3011 CGCCTGCCACTCTCAGCAA TTGCTGAGAGTGGCAGGCG 3012GCCTGCCACTCTCAGCAAG CTTGCTGAGAGTGGCAGGC 3013 CCTGCCACTCTCAGCAAGTACTTGCTGAGAGTGGCAGG 3014 CTGCCACTCTCAGCAAGTG CACTTGCTGAGAGTGGCAG 3015TGCCACTCTCAGCAAGTGC GCACTTGCTGAGAGTGGCA 3016 GCCACTCTCAGCAAGTGCGCGCACTTGCTGAGAGTGGC 3017 CCACTCTCAGCAAGTGCGG CCGCACTTGCTGAGAGTGG 3018CACTCTCAGCAAGTGCGGA TCCGCACTTGCTGAGAGTG 3019 ACTCTCAGCAAGTGCGGAGCTCCGCACTTGCTGAGAGT 3020 CTCTCAGCAAGTGCGGAGA TCTCCGCACTTGCTGAGAG 3021TCTCAGCAAGTGCGGAGAT ATCTCCGCACTTGCTGAGA 3022 CTCAGCAAGTGCGGAGATCGATCTCCGCACTTGCTGAG 3023 TCAGCAAGTGCGGAGATCG CGATCTCCGCACTTGCTGA 3024CAGCAAGTGCGGAGATCGC GCGATCTCCGCACTTGCTG 3025 AGCAAGTGCGGAGATCGCCGGCGATCTCCGCACTTGCT 3026 GCAAGTGCGGAGATCGCCT AGGCGATCTCCGCACTTGC 3027CAAGTGCGGAGATCGCCTC GAGGCGATCTCCGCACTTG 3028 AAGTGCGGAGATCGCCTCTAGAGGCGATCTCCGCACTT 3029 AGTGCGGAGATCGCCTCTG CAGAGGCGATCTCCGCACT 3030GTGCGGAGATCGCCTCTGG CCAGAGGCGATCTCCGCAC 3031 TGCGGAGATCGCCTCTGGGCCCAGAGGCGATCTCCGCA 3032 GCGGAGATCGCCTCTGGGA TCCCAGAGGCGATCTCCGC 3033CGGAGATCGCCTCTGGGAG CTCCCAGAGGCGATCTCCG 3034 GGAGATCGCCTCTGGGAGGCCTCCCAGAGGCGATCTCC 3035 GAGATCGCCTCTGGGAGGG CCCTCCCAGAGGCGATCTC 3036AGATCGCCTCTGGGAGGGG CCCCTCCCAGAGGCGATCT 3037 GATCGCCTCTGGGAGGGGATCCCCTCCCAGAGGCGATC 3038 ATCGCCTCTGGGAGGGGAG CTCCCCTCCCAGAGGCGAT 3039TCGCCTCTGGGAGGGGAGC GCTCCCCTCCCAGAGGCGA 3040 CGCCTCTGGGAGGGGAGCTAGCTCCCCTCCCAGAGGCG 3041 GCCTCTGGGAGGGGAGCTG CAGCTCCCCTCCCAGAGGC 3042CCTCTGGGAGGGGAGCTGC GCAGCTCCCCTCCCAGAGG 3043 CTCTGGGAGGGGAGCTGCATGCAGCTCCCCTCCCAGAG 3044 TCTGGGAGGGGAGCTGCAG CTGCAGCTCCCCTCCCAGA 3045CTGGGAGGGGAGCTGCAGC GCTGCAGCTCCCCTCCCAG 3046 TGGGAGGGGAGCTGCAGCATGCTGCAGCTCCCCTCCCA 3047 GGGAGGGGAGCTGCAGCAG CTGCTGCAGCTCCCCTCCC 3048GGAGGGGAGCTGCAGCAGG CCTGCTGCAGCTCCCCTCC 3049 GAGGGGAGCTGCAGCAGGATCCTGCTGCAGCTCCCCTC 3050 AGGGGAGCTGCAGCAGGAG CTCCTGCTGCAGCTCCCCT 3051GGGGAGCTGCAGCAGGAGG CCTCCTGCTGCAGCTCCCC 3052 GGGAGCTGCAGCAGGAGGATCCTCCTGCTGCAGCTCCC 3053 GGAGCTGCAGCAGGAGGAA TTCCTCCTGCTGCAGCTCC 3054GAGCTGCAGCAGGAGGAAG CTTCCTCCTGCTGCAGCTC 3055 AGCTGCAGCAGGAGGAAGATCTTCCTCCTGCTGCAGCT 3056 GCTGCAGCAGGAGGAAGAC GTCTTCCTCCTGCTGCAGC 3057CTGCAGCAGGAGGAAGACA TGTCTTCCTCCTGCTGCAG 3058 TGCAGCAGGAGGAAGACACGTGTCTTCCTCCTGCTGCA 3059 GCAGCAGGAGGAAGACACA TGTGTCTTCCTCCTGCTGC 3060CAGCAGGAGGAAGACACAG CTGTGTCTTCCTCCTGCTG 3061 AGCAGGAGGAAGACACAGCGCTGTGTCTTCCTCCTGCT 3062 GCAGGAGGAAGACACAGCC GGCTGTGTCTTCCTCCTGC 3063CAGGAGGAAGACACAGCCA TGGCTGTGTCTTCCTCCTG 3064 AGGAGGAAGACACAGCCACGTGGCTGTGTCTTCCTCCT 3065 GGAGGAAGACACAGCCACC GGTGGCTGTGTCTTCCTCC 3066GAGGAAGAGACAGCCACCA TGGTGGCTGTGTCTTCCTC 3067 AGGAAGACACAGCCACCAATTGGTGGCTGTGTCTTCCT 3068 GGAAGACACAGCCACCAAC GTTGGTGGCTGTGTCTTCC 3069GAAGACACAGCCACCAACT AGTTGGTGGCTGTGTCTTC 3070 AAGACACAGCCACCAACTCGAGTTGGTGGCTGTGTCTT 3071 AGACACAGCCACCAACTCC GGAGTTGGTGGCTGTGTCT 3072GACACAGCCACCAACTCCA TGGAGTTGGTGGCTGTGTC 3073 ACACAGCCACCAACTCCAGCTGGAGTTGGTGGCTGTGT 3074 CACAGCCACCAACTCCAGC GCTGGAGTTGGTGGCTGTG 3075ACAGCCACCAACTCCAGCT AGCTGGAGTTGGTGGCTGT 3076 CAGCCACCAACTCCAGCTCGAGCTGGAGTTGGTGGCTG 3077 AGCCACCAACTCCAGCTCT AGAGCTGGAGTTGGTGGCT 3078GCCACCAACTCCAGCTCTG CAGAGCTGGAGTTGGTGGC 3079 CCACCAACTCCAGCTCTGATCAGAGCTGGAGTTGGTGG 3080 CACCAACTCCAGCTCTGAG CTCAGAGCTGGAGTTGGTG 3081ACCAACTCCAGCTCTGAGG CCTCAGAGCTGGAGTTGGT 3082 CCAACTCCAGCTCTGAGGATCCTCAGAGCTGGAGTTGG 3083 CAACTCCAGCTCTGAGGAA TTCCTCAGAGCTGGAGTTG 3084AACTCCAGCTCTGAGGAAG CTTCCTCAGAGCTGGAGTT 3085 ACTCCAGCTCTGAGGAAGGCCTTCCTCAGAGCTGGAGT 3086 CTCCAGCTCTGAGGAAGGC GCCTTCCTCAGAGCTGGAG 3087TCCAGCTCTGAGGAAGGCC GGCCTTCCTCAGAGCTGGA 3088 CCAGCTCTGAGGAAGGCCCGGGCCTTCCTCAGAGCTGG 3089 CAGCTCTGAGGAAGGCCCA TGGGCCTTCCTCAGAGCTG 3090AGCTCTGAGGAAGGCCCAG CTGGGCCTTCCTCAGAGCT 3091 GCTCTGAGGAAGGCCCAGGCCTGGGCCTTCCTCAGAGC 3092 CTCTGAGGAAGGCCCAGGG CCCTGGGCCTTCCTCAGAG 3093TCTGAGGAAGGCCCAGGGT ACCCTGGGCCTTCCTCAGA 3094 CTGAGGAAGGCCCAGGGTCGACCCTGGGCCTTCCTCAG 3095 TGAGGAAGGCCCAGGGTCC GGACCCTGGGCCTTCCTCA 3096GAGGAAGGCCCAGGGTCCG CCGACCCTGGGCCTTCCTC 3097 AGGAAGGCCCAGGGTCCGGCCGGACCCTGGGCCTTCCT 3098 GGAAGGCCCAGGGTCCGGC GCCGGACCCTGGGCCTTCC 3099GAAGGCCCAGGGTCCGGCC GGCCGGACCCTGGGCCTTC 3100 AAGGCCCAGGGTCCGGCCCGGGCCGGACCCTGGGCCTT 3101 AGGCCCAGGGTCCGGCCCT AGGGCCGGACCCTGGGCCT 3102GGCCCAGGGTCCGGCCCTG CAGGGCCGGACCCTGGGCC 3103 GCCCAGGGTCCGGCCCTGATCAGGGCCGGACCCTGGGC 3104 CCCAGGGTCCGGCCCTGAC GTCAGGGCCGGACCCTGGG 3105CCAGGGTCCGGCCCTGACA TGTCAGGGCCGGACCCTGG 3106 CAGGGTCCGGCCCTGACAGCTGTCAGGGCCGGACCCTG 3107 AGGGTCCGGCCCTGACAGC GCTGTCAGGGCCGGACCCT 3108GGGTCCGGCCCTGACAGCG GGCTGTCAGGGCCGGACCC 3109 GGTCCGGCCCTGACAGCCGCGGCTGTCAGGGCCGGACC 3110 GTCCGGCCCTGACAGCCGG CCGGCTGTCAGGGCCGGAC 3111TCCGGCCCTGACAGCCGGC GCCGGCTGTCAGGGCCGGA 3112 CCGGCCCTGACAGCCGGCTAGCCGGCTGTCAGGGCCGG 3113 CGGCCCTGACAGCCGGCTC GAGCCGGCTGTCAGGGCCG 3114GGCCCTGACAGCCGGCTCA TGAGCCGGCTGTCAGGGCC 3115 GCCCTGACAGCCGGCTCAGCTGAGCCGGCTGTCAGGGC 3116 CCCTGACAGCCGGCTCAGC GCTGAGCCGGCTGTCAGGG 3117CCTGACAGCCGGCTCAGCA TGCTGAGCCGGCTGTCAGG 3118 CTGACAGCCGGCTCAGCACGTGCTGAGCCGGCTGTCAG 3119 TGACAGCCGGCTCAGCACA TGTGCTGAGCCGGCTGTCA 3120GACAGCCGGCTCAGCACAG CTGTGCTGAGCCGGCTGTC 3121 ACAGCCGGCTCAGCACAGGCCTGTGCTGAGCCGGCTGT 3122 CAGCCGGCTCAGCACAGGC GCCTGTGCTGAGCCGGCTG 3123AGCCGGCTCAGCACAGGCC GGCCTGTGCTGAGCCGGCT 3124 GCCGGCTCAGCACAGGCCTAGGCCTGTGCTGAGCCGGC 3125 CCGGCTCAGCACAGGCCTC GAGGCCTGTGCTGAGCCGG 3126CGGCTCAGCACAGGCCTCG CGAGGCCTGTGCTGAGCCG 3127 GGCTCAGCACAGGCCTCGCGCGAGGCCTGTGCTGAGCC 3128 GCTCAGCACAGGCCTCGCC GGCGAGGCCTGTGCTGAGC 3129CTCAGCACAGGCCTCGCCA TGGCGAGGCCTGTGCTGAG 3130 TCAGCACAGGCCTCGCCAATTGGCGAGGCCTGTGCTGA 3131 CAGCACAGGCCTCGCCAAG CTTGGCGAGGCCTGTGCTG 3132AGCACAGGCCTCGCCAAGC GCTTGGCGAGGCCTGTGCT 3133 GCACAGGCCTCGCCAAGCATGCTTGGCGAGGCCTGTGC 3134 CACAGGCCTCGCCAAGCAC GTGCTTGGCGAGGCCTGTG 3135ACAGGCCTCGCCAAGCACC GGTGCTTGGCGAGGCCTGT 3136 CAGGCCTCGCCAAGCACCTAGGTGCTTGGCGAGGCCTG 3137 AGGCCTCGCCAAGCACCTG CAGGTGCTTGGCGAGGCCT 3138GGCCTCGCCAAGCACCTGC GCAGGTGCTTGGCGAGGCC 3139 GCCTCGCCAAGCACCTGCTAGCAGGTGCTTGGCGAGGC 3140 CCTCGCCAAGCACCTGCTC GAGCAGGTGCTTGGCGAGG 3141CTCGCCAAGCACCTGCTCA TGAGCAGGTGCTTGGCGAG 3142 TCGCCAAGCACCTGCTCAGCTGAGCAGGTGCTTGGCGA 3143 CGCCAAGCACCTGCTCAGT ACTGAGCAGGTGCTTGGCG 3144GCCAAGCACCTGCTCAGTG CACTGAGCAGGTGCTTGGC 3145 CCAAGCACCTGCTCAGTGGCCACTGAGCAGGTGCTTGG 3146 CAAGCACCTGCTCAGTGGT ACCACTGAGCAGGTGCTTG 3147AAGCACCTGCTCAGTGGTT AACCACTGAGCAGGTCCTT 3148 AGCACCTGCTCAGTGGTTTAAACCACTGAGCAGGTGCT 3149 GCACCTGCTCAGTGGTTTG CAAACCACTGAGCAGGTGC 3150CACCTGCTCAGTGGTTTGG CCAAACCACTGAGCAGGTG 3151 ACCTGCTCAGTGGTTTGGGCCCAAACCACTGAGCAGGT 3152 CCTGCTCAGTGGTTTGGGG CCCCAAACCACTGAGCAGG 3153CTGCTCAGTGGTTTGGGGG CCCCCAAACCACTGAGCAG 3154 TGCTCAGTGGTTTGGGGGATCCCCCAAACCACTGAGCA 3155 GCTCAGTGGTTTGGGGGAC GTCCCCCAAACCACTGAGC 3156CTCAGTGGTTTGGGGGACC GGTCCCCCAAACCACTGAG 3157 TCAGTGGTTTGGGGGACCGCGGTCCCCCAAACCACTGA 3158 CAGTGGTTTGGGGGACCGA TCGGTCCCCCAAACCACTG 3159AGTGGTTTGGGGGACCGAC GTCGGTCCCCCAAACCACT 3160 GTGGTTTGGGGGACCGACTAGTCGGTCCCCCAAACCAC 3161 TGGTTTGGGGGACCGACTG CAGTCGGTCCCCCAAACCA 3162GGTTTGGGGGACCGACTGT ACAGTCGGTCCCCCAAACC 3163 GTTTGGGGGACCGACTGTGCACAGTCGGTCCCCCAAAC 3164 TTTGGGGGACCGACTGTGC GCACAGTCGGTCCCCCAAA 3165TTGGGGGACCGACTGTGCC GGCACAGTCGGTCCCCCAA 3166 TGGGGGACCGACTGTGCCGCGGCACAGTCGGTCCCCCA 3167 GGGGGACCGACTGTGCCGC GCGGCACAGTCGGTCCCCC 3168GGGGACCGACTGTGCCGCC GGCGGCACAGTCGGTCCCC 3169 GGGACCGACTGTGCCGCCTAGGCGGCACAGTCGGTCCC 3170 GGACCGACTGTGCCGCCTG CAGGCGGCACAGTCGGTCC 3171GACCGACTGTGCCGCCTGC GCAGGCGGCACAGTCGGTC 3172 ACCGACTGTGCCGCCTGCTAGCAGGCGGCACAGTCGGT 3173 CCGACTGTGCCGCCTGCTG CAGCAGGCGGCACAGTCGG 3174CGACTGTGCCGCCTGCTGC GCAGCAGGCGGCACAGTCG 3175 GACTGTGCCGCCTGCTGCGCGCAGCAGGCGGCACAGTC 3176 ACTGTGCCGCCTGCTGCGG CCGCAGCAGGCGGCACAGT 3177CTGTGCCGCCTGCTGCGGA TCCGCAGCAGGCGGCACAG 3178 TGTGCCGCCTGCTGCGGAGCTCCGCAGCAGGCGGCACA 3179 GTGCCGCCTGCTGCGGAGG CCTCCGCAGCAGGCGGCAC 3180TGCCGCCTGCTGCGGAGGG CCCTCCGCAGCAGGCGGCA 3181 GCCGCCTGCTGCGGAGGGATCCCTCCGCAGCAGGCGGC 3182 CCGCCTGCTGCGGAGGGAG CTCCCTCCGCAGCAGGCGG 3183CGCCTGCTGCGGAGGGAGC GCTCCCTCCGCAGCAGGCG 3184 GCCTGCTGCGGAGGGAGCGCGCTCCCTCCGCAGCAGGC 3185 CCTGCTGCGGAGGGAGCGG CCGCTCCCTCCGCAGCAGG 3186CTGCTGCGGAGGGAGCGGG CCCGCTCCGTCCGCAGCAG 3187 TGCTGCGGAGGGAGCGGGATCCCGCTCCCTCCGCAGCA 3188 GCTGCGGAGGGAGCGGGAG CTCCCGCTCCCTCCGCAGC 3189CTGCGGAGGGAGCGGGAGG CCTCCCGCTCCCTCCGCAG 3190 TGCGGAGGGAGCGGGAGGCGCCTCCCGCTCCCTCCGCA 3191 GCGGAGGGAGCGGGAGGCC GGCCTCCCGCTCCCTCCGC 3192CGGAGGGAGCGGGAGGCCC GGGCCTCCCGCTCCCTCCG 3193 GGAGGGAGCGGGAGGCCCTAGGGCCTCCCGCTCCCTCC 3194 GAGGGAGCGGGAGGCCCTG CAGGGCCTCCCGCTCCCTC 3195AGGGAGCGGGAGGCCCTGG CCAGGGCCTCCCGCTCCCT 3196 GGGAGCGGGAGGCCCTGGCGCCAGGGCCTCCCGCTCCC 3197 GGAGCGGGAGGCCCTGGCT AGCCAGGGCCTCCCGCTCC 3198GAGCGGGAGGCCCTGGCTT AAGCCAGGGCCTCCCGCTC 3199 AGCGGGAGGCCCTGGCTTGCAAGCCAGGGCCTCCCGCT 3200 GCGGGAGGCCCTGGCTTGG CCAAGCCAGGGCCTCCCGC 3201CGGGAGGCCCTGGCTTGGG CCCAAGCCAGGGCCTCCCG 3202 GGGAGGCCCTGGCTTGGGCGCCCAAGCCAGGGCCTCCC 3203 GGAGGCCCTGGCTTGGGCC GGCCCAAGCCAGGGCCTCC 3204GAGGCCCTGGCTTGGGCCC GGGCCCAAGCCAGGGCCTC 3205 AGGCCCTGGCTTGGGCCCATGGGCCCAAGCCAGGGCCT 3206 GGCCCTGGCTTGGGCCCAG CTGGGCCCAAGCCAGGGCC 3207GCCCTGGCTTGGGCCCAGC GCTGGGCCCAAGCCAGGGC 3208 CCCTGGCTTGGGCCCAGCGCGCTGGGCCCAAGCCAGGG 3209 CCTGGCTTGGGCCCAGCGG CCGCTGGGCCCAAGCCAGG 3210CTGGCTTGGGCCCAGCGGG CCCGCTGGGCCCAAGCCAG 3211 TGGCTTGGGCCCAGCGGGATCCCGCTGGGCCCAAGCCA 3212 GGCTTGGGCCCAGCGGGAA TTCCCGCTGGGCCCAAGCC 3213GCTTGGGCCCAGCGGGAAG CTTCCCGCTGGGCCCAAGC 3214 CTTGGGCCCAGCGGGAAGGCCTTCCCGCTGGGCCCAAG 3215 TTGGGCCCAGCGGGAAGGC GCCTTCCCGCTGGGCCCAA 3216TGGGCCCAGCGGGAAGGCC GGCCTTCCCGCTGGGCCCA 3217 GGGCCCAGCGGGAAGGCCATGGCCTTCCCGCTGGGCCC 3218 GGCCCAGCGGGAAGGCCAA TTGGCCTTCCCGCTGGGCC 3219GCCCAGCGGGAAGGCCAAG CTTGGCCTTCCCGCTGGGC 3220 CCCAGCGGGAAGGCCAAGGCCTTGGCCTTCCCGCTGGG 3221 CCAGCGGGAAGGCCAAGGG CCCTTGGCCTTCCCGCTGG 3222CAGCGGGAAGGCCAAGGGC GCCCTTGGCCTTCCCGCTG 3223 AGCGGGAAGGCCAAGGGCCGGCCCTTGGCCTTCCCGCT 3224 GCGGGAAGGCCAAGGGCCA TGGCCCTTGGCCTTCCCGC 3225CGGGAAGGCCAAGGGCCAG CTGGCCCTTGGCCTTCCCG 3226 GGGAAGGCCAAGGGCCAGCGCTGGCCCTTGGCCTTCCC 3227 GGAAGGCCAAGGGCCAGCC GGCTGGCCCTTGGCCTTCC 3228GAAGGCCAAGGGCCAGCCG CGGCTGGCCCTTGGCCTTC 3229 AAGGCCAAGGGCCAGCCGTACGGCTGGCCCTTGGCCTT 3230 AGGCCAAGGGCCAGCCGTG CACGGCTGGCCCTTGGCCT 3231GGCCAAGGGCCAGCCGTGA TCACGGCTGGCCCTTGGCC 3232 GCCAAGGGCCAGCCGTGACGTCACGGCTGGCCCTTGGC 3233 CCAAGGGCCAGCCGTGACA TGTCACGGCTGGCCCTTGG 3234CAAGGGCCAGCCGTGACAG CTGTCACGGCTGGCCCTTG 3235 AAGGGCCAGCCGTGACAGATCTGTCACGGCTGGCCCTT 3236 AGGGCCAGCCGTGACAGAG CTCTGTCACGGCTGGCCCT 3237GGGCCAGCCGTGACAGAGG CCTCTGTCACGGCTGGCCC 3238 GGCCAGCCGTGACAGAGGATCCTCTGTCACGGCTGGCC 3239 GCCAGCCGTGACAGAGGAC GTCCTCTGTCACGGCTGGC 3240CCAGCCGTGACAGAGGACA TGTCCTCTGTCACGGCTGG 3241 CAGCCGTGACAGAGGACAGCTGTCCTCTGTCACGGCTG 3242 AGCCGTGACAGAGGACAGC GCTGTCCTCTGTCACGGCT 3243GCCGTGACAGAGGACAGCC GGCTGTCCTCTGTCACGGC 3244 CCGTGACACAGGACAGCCCGGGCTGTCCTCTGTCACGG 3245 CGTGACAGAGGACAGCCCA TGGGCTGTCCTCTGTCACG 3246GTGACAGAGGACAGCCCAG CTGGGCTGTCCTCTGTCAC 3247 TGACAGAGGACAGCCCAGGCCTGGGCTGTCCTCTGTCA 3248 GACAGAGGACAGCCCAGGC GCCTGGGCTGTCCTCTGTC 3249ACAGAGGACAGCCCAGGCA TGCCTGGGCTGTCCTCTGT 3250 CAGAGGACAGCCCAGGCATATGCCTGGGCTGTCCTCTG 3251 AGAGGACAGCCCAGGCATT AATGCCTGGGCTGTCCTCT 3252GAGGACAGCCCAGGCATTC GAATGCCTGGGCTGTCCTC 3253 AGGACAGCCCAGGCATTCCGGAATGCCTGGGCTGTCCT 3254 GGACAGCCCAGGCATTCCA TGGAATGCCTGGGCTGTCC 3255GACAGCCCAGGCATTCCAC GTGGAATGCCTGGGCTGTC 3256 ACAGCCCAGGCATTCCACGCGTGGAATGCCTGGGCTGT 3257 CAGCCCAGGCATTCCACGC GCGTGGAATGCCTGGGCTG 3258AGCCCAGGCATTCCACGCT AGCGTGGAATGCCTGGGCT 3259 GCCCAGGCATTCCACGCTGCAGCGTGGAATGCCTGGGC 3260 CCCAGGCATTCCACGCTGC GCAGCGTGGAATGCCTGGG 3261CCAGGCATTCCACGCTGCT AGCAGCGTGGAATGCCTGG 3262 CAGGCATTCCACGCTGCTGCAGCAGCGTGGAATGCCTG 3263 AGGCATTCCACGCTGCTGC GCAGCAGCGTGGAATGCCT 3264GGCATTCCACGCTGCTGCA TGCAGCAGCGTGGAATGCC 3265 GCATTCCACGCTGCTGCAGCTGCAGCAGCGTGGAATGC 3266 CATTCCACGCTGCTGCAGC GCTGCAGCAGCGTGGAATG 3267ATTCCACGCTGCTGCAGCC GGCTGCAGCAGCGTGGAAT 3268 TTCCACGCTGCTGCAGCCGCGGCTGCAGCAGCGTGGAA 3269 TCCACGCTGCTGCAGCCGT ACGGCTGCAGCAGCGTGGA 3270CCACGCTGCTGCAGCCGTT AACGGCTGCAGCAGCGTGG 3271 CACGCTGCTGCAGCCGTTGCAACGGCTGCAGCAGCGTG 3272 ACGCTGCTGCAGCCGTTGC GCAACGGCTGCAGCAGCGT 3273CGCTGCTGCAGCCGTTGCC GGCAACGGCTGCAGCAGCG 3274 GCTGCTGCAGCCGTTGCCATGGCAACGGCTGCAGCAGC 3275 CTGCTGCAGCCGTTGCCAC GTGGCAACGGCTGCAGCAG 3276TGCTGCAGCCGTTGCCACC GGTGGCAACGGCTGCAGCA 3277 GCTGCAGCCGTTGCCACCATGGTGGCAACGGCTGCAGC 3278 CTGCAGCCGTTGCCACCAT ATGGTGGCAACGGCTGCAG 3279TGCAGCCGTTGCCACCATG CATGGTGGCAACGGCTGCA 3280 GCAGCCGTTGCCACCATGGCCATGGTGGCAACGGCTGC 3281 CAGCCGTTGCCACCATGGA TCCATGGTGGCAACGGCTG 3282AGCCGTTGCCACCATGGAC GTCCATGGTGGCAACGGCT 3283 GCCGTTGCCACCATGGACTAGTCCATGGTGGCAAGGGC 3284 CCGTTGCCACCATGGACTC GAGTCCATGGTGGCAACGG 3285CGTTGCCACCATGGACTCT AGAGTCCATGGTGGCAACG 3286 GTTGCCACCATGGACTCTTAAGAGTCCATGGTGGCAAC 3287 TTGCCACCATGGACTCTTC GAAGAGTCCATGGTGGCAA 3288TGCCACCATGGACTCTTCA TGAAGAGTCCATGGTGGCA 3289 GCCACCATGGACTCTTCAATTGAAGAGTCCATGGTGGC 3290 CCACCATGGACTCTTCAAC GTTGAAGAGTCCATGGTGG 3291CACCATGGACTCTTCAACA TGTTGAAGAGTCCATGGTG 3292 ACCATGGACTCTTCAACACGTGTTGAAGAGTCCATGGT 3293 CCATGGACTCTTCAACACC GGTGTTGAAGAGTCCATGG 3294CATGGACTCTTCAACACCC GGGTGTTGAAGAGTCCATG 3295 ATGGACTCTTCAACACCCATGGGTGTTGAAGAGTCCAT 3296 TGGACTCTTCAACACCCAC GTGGGTGTTGAAGAGTCCA 3297GGACTCTTCAACACCCACT AGTGGGTGTTGAAGAGTCC 3298 GACTCTTCAACACCCACTGCAGTGGGTGTTGAAGAGTC 3299 ACTCTTCAACACCCACTGG CCAGTGGGTGTTGAAGAGT 3300CTCTTCAACACCCACTGGC GCCAGTGGGTGTTGAAGAG 3301 TCTTCAACACCCACTGGCGCGCCAGTGGGTGTTGAAGA 3302 CTTCAACACCCACTGGCGA TCGCCAGTGGGTGTTGAAG 3303TTCAACACCCACTGGCGAT ATCGCCAGTGGGTGTTGAA 3304 TCAACACCCACTGGCGATGCATCGCCAGTGGGTGTTGA 3305 CAACACCCACTGGCGATGT ACATCGCCAGTGGGTGTTG 3306AACACCCACTGGCGATGTC GACATCGCCAGTGGGTGTT 3307 ACACCCACTGGCGATGTCCGGACATCGCCAGTGGGTGT 3308 CACCCACTGGCGATGTCCC GGGACATCGCCAGTGGGTG 3309ACCCACTGGCGATGTCCCC GGGGACATCGCCAGTGGGT 3310 CCCACTGGCGATGTCCCCGCGGGGACATCGCCAGTGGG 3311 CCACTGGCGATGTCCCCGC GCGGGGACATCGCCAGTGG 3312CACTGGCGATGTCCCCGCT AGCGGGGACATCGCCAGTG 3313 ACTGGCGATGTCCCCGCTGCAGCGGGGACATCGCCAGT 3314 CTGGCGATGTCCCCGCTGC GCAGCGGGGACATCGCCAG 3315TGGCGATGTCCCCGCTGCA TGCAGCGGGGACATCGCCA 3316 GGCGATGTCCCCGCTGCAGCTGCAGCGGGGACATCGCC 3317 GCGATGTCCCCGCTGCAGC GCTGCAGCGGGGACATCGC 3318CGATGTCCCCGCTGCAGCC GGCTGCAGCGGGGACATCG 3319 GATGTCCCCGCTGCAGCCATGGCTGCAGCGGGGACATC 3320 ATGTCCCCGCTGCAGCCAC GTGGCTGCAGCGGGGACAT 3321TGTCCCCGCTGCAGCCACC GGTGGCTGCAGCGGGGACA 3322 GTCCCCGCTGCAGCCACCGCGGTGGCTGCAGCGGGGAC 3323 TCCCCGCTGCAGCCACCGG CCGGTGGCTGCAGCGGGGA 3324CCCCGCTGCAGCCACCGGC GCCGGTGGCTGCAGCGGGG 3325 CCCGCTGCAGCCACCGGCTAGCCGGTGGCTGCAGCGGG 3326 CCGCTGCAGCCACCGGCTG CAGCCGGTGGCTGCAGCGG 3327CGCTGCAGCCACCGGCTGT ACAGCCGGTGGCTGCAGCG 3328 GCTGCAGCCACCGGCTGTGCACAGCCGGTGGCTGCAGC 3329 CTGCAGCCACCGGCTGTGT ACACAGCCGGTGGCTGCAG 3330TGCAGCCACCGGCTGTGTG CACACAGCCGGTGGCTGCA 3331 GCAGCCACCGGCTGTGTGTACACACAGCCGGTGGCTGC 3332 CAGCCACCGGCTGTGTGTG CACACACAGCCGGTGGCTG 3333AGCCACCGGCTGTGTGTGG CCACACACAGCCGGTGGCT 3334 GCCACCGGCTGTGTGTGGCGCCACACACAGCCGGTGGC 3335 CCACCGGCTGTGTGTGGCC GGCCACACACAGCCGGTGG 3336CACCGGCTGTGTGTGGCCT AGGCCACACACAGCCGGTG 3337 ACCGGCTGTGTGTGGCCTGCAGGCCACACACAGCCGGT 3338 CCGGCTGTGTGTGGCCTGT ACAGGCCACACACAGCCGG 3339CGGCTGTGTGTGGCCTGTG CACAGGCCACACACAGCCG 3340 GGCTGTGTGTGGCCTGTGGCCACAGGCCACACACAGCC 3341 GCTGTGTGTGGCCTGTGGT ACCACAGGCCACACACAGC 3342CTGTGTGTGGCCTGTGGTC GACCACAGGCCACACACAG 3343 TGTGTGTGGCCTGTGGTCGCGACCACAGGCCACACACA 3344 GTGTGTGGCCTGTGGTCGT ACGACCACAGGCCACACAC 3345TGTGTGGCCTGTGGTCGTG CACGACCACAGGCCACACA 3346 GTGTGGCCTGTGGTCGTGTACACGACCACAGGCCACAC 3347 TGTGGCCTGTGGTCGTGTG CACACGACCACAGGCCACA 3348GTGGCCTGTGGTCGTGTGG CCACACGACCACAGGCCAC 3349 TGGCCTGTGGTCGTGTGGCGCCACACGACCACAGGCCA 3350 GGCCTGTGGTCGTGTGGCA TGCCACACGACCACAGGCC 3351GCCTGTGGTCGTGTGGCAG CTGCCACACGACCACAGGC 3352 CCTGTGGTCGTGTGGCAGGCCTGCCACACGACCACAGG 3353 CTGTGGTCGTGTGGCAGGC GCCTGCCACACGACCACAG 3354TGTGGTCGTGTGGCAGGCA TGCCTGCCACACGACCACA 3355 GTGGTCGTGTGGCAGGCACGTGCCTGCCACACGACCAC 3356 TGGTCGTGTGGCAGGCACT AGTGCCTGCCACACGACCA 3357GGTCGTGTGGCAGGCACTG CAGTGCCTGCCACACGACC 3358 GTCGTGTGGCAGGCACTGGCCAGTGCCTGCCACACGAC 3359 TCGTGTGGCAGGCACTGGG CCCAGTGCCTGCCACACGA 3360CGTGTGGCAGGCACTGGGC GCCCAGTGCCTGCCACACG 3361 GTGTGGCAGGCACTGGGCGCGCCCAGTGCCTGCCACAC 3362 TGTGGCAGGCACTGGGCGG CCGCCCAGTGCCTGCCACA 3363GTGGCAGGCACTGGGCGGG CCCGCCCAGTGCCTGCCAC 3364 TGGCAGGCACTGGGCGGGCGCCCGCCCAGTGCCTGCCA 3365 GGCAGGCACTGGGCGGGCC GGCCCGCCCAGTGCCTGCC 3366GCAGGCACTGGGCGGGCCA TGGCCCGCCCAGTGCCTGC 3367 CAGGCACTGGGCGGGCCAGCTGGCCCGCCCAGTGCCTG 3368 AGGCACTGGGCGGGCCAGG CCTGGCCCGCCCAGTGCCT 3369GGCACTGGGCGGGCCAGGG CCCTGGCCCGCCCAGTGCC 3370 GCACTGGGCGGGCCAGGGATCCCTGGCCCGCCCAGTGC 3371 CACTGGGCGGGCCAGGGAG CTCCCTGGCCCGCCCAGTG 3372ACTGGGCGGGCCAGGGAGA TCTCCCTGGCCCGCCCAGT 3373 CTGGGCGGGCCAGGGAGAATTCTCCCTGGCCCGCCCAG 3374 TGGGCGGGCCAGGGAGAAA TTTCTCCCTGGCCCGCCCA 3375GGGCGGGCCAGGGAGAAAG CTTTCTCCCTGGCCCGCCC 3376 GGCGGGCCAGGGAGAAAGCGCTTTCTCCCTGGCCCGCC 3377 GCGGGCCAGGGAGAAAGCA TGCTTTCTCCCTGGCCCGC 3378CGGGCCAGGGAGAAAGCAG CTGCTTTCTCCCTGGCCCG 3379 GGGCCAGGGAGAAAGCAGGCCTGCTTTCTCCCTGGCCC 3380 GGCCAGGGAGAAAGCAGGC GCCTGCTTTCTCCCTGGCC 3381GCCAGGGAGAAAGCAGGCT AGCCTGCTTTCTCCCTGGC 3382 CCAGGGAGAAAGCAGGCTTAAGCCTGCTTTCTCCCTGG 3383 CAGGGAGAAAGCAGGCTTT AAAGCCTGCTTTCTCCCTG 3384AGGGAGAAAGCAGGCTTTC GAAAGCCTGCTTTCTCCCT 3385 GGGAGAAAGCAGGCTTTCATGAAAGCCTGCTTTCTCCC 3386 GGAGAAAGCAGGCTTTCAG CTGAAAGCCTGCTTTCTCC 3387GAGAAAGCAGGCTTTCAGG CCTGAAAGCCTGCTTTCTC 3388 AGAAAGCAGGCTTTCAGGATCCTGAAAGCCTGCTTTCT 3389 GAAAGCAGGCTTTCAGGAG CTCCTGAAAGCCTGCTTTC 3390AAAGCAGGCTTTCAGGAGC GCTCCTGAAAGCCTGCTTT 3391 AAGCAGGCTTTCAGGAGCATGCTCCTGAAAGCCTGCTT 3392 AGCAGGCTTTCAGGAGCAG CTGCTCCTGAAAGCCTGCT 3393GCAGGCTTTCAGGAGCAGT ACTGCTCCTGAAAGCCTGC 3394 CAGGCTTTCAGGAGCAGTCGACTGCTCCTGAAAGCCTG 3395 AGGCTTTCAGGAGCAGTCC GGACTGCTCCTGAAAGCCT 3396GGCTTTCAGGAGCAGTCCG CGGACTGCTCCTGAAAGCC 3397 GCTTTCAGGAGCAGTCCGCGCGGACTGCTCCTGAAAGC 3398 CTTTCAGGAGCAGTCCGCG CGCGGACTGCTCCTGAAAG 3399TTTCAGGAGCAGTCCGCGG CCGCGGACTGCTCCTGAAA 3400 TTCAGGAGCAGTCCGCGGATCCGCGGACTGCTCCTGAA 3401 TCAGGAGCAGTCCGCGGAG CTCCGCGGACTGCTCCTGA 3402CAGGAGCAGTCCGCGGAGG CCTCCGCGGACTGCTCCTG 3403 AGGAGCAGTCCGCGGAGGATCCTCCGCGGACTGCTCCT 3404 GGAGCAGTCCGCGGAGGAG CTCCTCCGCGGACTGCTCC 3405GAGCAGTCCGCGGAGGAGT ACTCCTCCGCGGACTGCTC 3406 AGCAGTCCGCGGAGGAGTGCACTCCTCCGCGGACTGCT 3407 GCAGTCCGCGGAGGAGTGC GCACTCCTCCGCGGACTGC 3408CAGTCCGCGGAGGAGTGCA TGCACTCCTCCGCGGACTG 3409 AGTCCGCGGAGGAGTGCACGTGCACTCCTCCGCGGACT 3410 GTCCGCGGAGGAGTGCACG CGTGCACTCCTCCGCGGAC 3411TCCGCGGAGGAGTGCACGC GCGTGCACTCCTCCGCGGA 3412 CCGCGGAGGAGTGCACGCATGCGTGCACTCCTCCGCGG 3413 CGCGGAGGAGTGCACGCAG CTGCGTGCACTCCTCCGCG 3414GCGGAGGAGTGCACGCAGG CCTGCGTGCACTCCTCCGC 3415 CGGAGGAGTGCACGCAGGATCCTGCGTGCACTCCTCCG 3416 GGAGGAGTGCACGCAGGAG CTCCTGCGTGCACTCCTCC 3417GAGGAGTGCACGCAGGAGG CCTCCTGCGTGCACTCCTC 3418 AGGAGTGCACGCAGGAGGCGCCTCCTGCGTGCACTCCT 3419 GGAGTGCACGCAGGAGGCC GGCCTCCTGCGTGCACTCC 3420GAGTGCACGCAGGAGGCCG CGGCCTCCTGCGTGCACTC 3421 AGTGCACGCAGGAGGCCGGCCGGCCTCCTGCGTGCACT 3422 GTGCACGCAGGAGGCCGGG CCCGGCCTCCTGCGTGCAC 3423TGCACGCAGGAGGCCGGGC GCCCGGCCTCCTGCGTGCA 3424 GCACGCAGGAGGCCGGGCATGCCCGGCCTCCTGCGTGC 3425 CACGCAGGAGGCCGGGCAC GTGCCCGGCCTCCTGCGTC 3426ACGCAGGAGGCCGGGCACC CGTGCCCGGCCTCCTGCGT 3427 CGCAGGAGGCCGGGCACGCGCGTGCCCGGCCTCCTGCG 3428 GCAGGAGGCCGGGCACGCT AGCGTGCCCGGCCTCCTGC 3429CAGGAGGCCGGGCACGCTG CAGCGTGCCCGGCCTCCTG 3430 AGGAGGCCGGGCACGCTGCGCAGCGTGCCCGGCCTCCT 3431 GGAGGCCGGGCACGCTGCC GGCAGCGTGCCCGGCCTCC 3432GAGGCCGGGCACGCTGCCT AGGCAGCGTGCCCGGCCTC 3433 AGGCCGGGCACGCTGCCTGCAGGCAGCGTGCCCGGCCT 3434 GGCCGGGCACGCTGCCTGT ACAGGCAGCGTGCCCGGCC 3435GCCGGGCACGCTGCCTGTT AACAGGCAGCGTGCCCGGC 3436 CCGGGCACGCTGCCTGTTCGAACAGGCAGCGTGCCCGG 3437 CGGGCACGCTGCCTGTTCC GGAACAGGCAGCGTGCCCG 3438GGGCACGCTGCCTGTTCCC GGGAACAGGCAGCGTGCCC 3439 GGCACGCTGCCTGTTCCCTAGGGAACAGGCAGCGTGCC 3440 GCACGCTGCCTGTTCCCTG CAGGGAACAGGCAGCGTGC 3441CACGCTGCCTGTTCCCTGA TCAGGGAACAGGCAGCGTG 3442 ACGCTGCCTGTTCCCTGATATCAGGGAACAGGCAGCGT 3443 CGCTGCCTGTTCCCTGATG CATCAGGGAACAGGCAGCG 3444GCTGCCTGTTCCCTGATGC GCATCAGGGAACAGGCAGC 3445 CTGCCTGTTCCCTGATGCTAGCATCAGGGAACAGGCAG 3446 TGCCTGTTCCCTGATGCTG CAGCATCAGGGAACAGGCA 3447GCCTGTTCCCTGATGCTGA TCAGCATCAGGGAACAGGC 3448 CCTGTTCCCTGATGCTGACGTCAGCATCAGGGAACAGG 3449 CTGTTCCCTGATGCTGACC GGTCAGCATCAGGGAACAG 3450TGTTCCCTGATGCTGACCC GGGTCAGCATCAGGGAACA 3451 GTTCCCTGATGCTGACCCATGGGTCAGCATCAGGGAAC 3452 TTCCCTGATGCTGACCCAG CTGGGTCAGCATCAGGGAA 3453TCCCTGATGCTGACCCAGT ACTGGGTCAGCATCAGGGA 3454 CCCTGATGCTGACCCAGTTAACTGGGTCAGCATCAGGG 3455 CCTGATGCTGACCCAGTTT AAACTGGGTCAGCATCAGG 3456CTGATGCTGACCCAGTTTG CAAACTGGGTCAGCATCAG 3457 TGATGCTGACCCAGTTTGTACAAACTGGGTCAGCATCA 3458 GATGCTGACCCAGTTTGTC GACAAACTGGGTCAGCATC 3459ATGCTGACCCAGTTTGTCT AGACAAACTGGGTCAGCAT 3460 TGCTGACCCAGTTTGTCTCGAGACAAACTGGGTCAGCA 3461 GCTGACCCAGTTTGTCTCC GGAGACAAACTGGGTCAGC 3462CTGACCCAGTTTGTCTCCA TGGAGACAAACTGGGTCAG 3463 TGACCCAGTTTGTCTCCAGCTGGAGACAAACTGGGTCA 3464 GACCCAGTTTGTCTCCAGC GCTGGAGACAAACTGGGTC 3465ACCCAGTTTGTCTCCAGCC GGCTGGAGACAAACTGGGT 3466 CCCAGTTTGTCTCCAGCCATGGCTGGAGACAAACTGGG 3467 CCAGTTTGTCTCCAGCCAG CTGGCTGGAGACAAACTGG 3468CAGTTTGTCTCCAGCCAGG CCTGGCTGGAGACAAACTG 3469 AGTTTGTCTCCAGCCAGGCGCCTGGCTGGAGACAAACT 3470 GTTTGTCTCCAGCCAGGCT AGCCTGGCTGGAGACAAAC 3471TTTGTCTCCAGCCAGGCTT AAGCCTGGCTGGAGACAAA 3472 TTGTCTCCAGCCAGGCTTTAAAGCCTGGCTGGAGACAA 3473 TGTCTCCAGCCAGGCTTTG CAAAGCCTGGCTGGAGACA 3474GTCTCCAGCCAGGCTTTGG CCAAAGCCTGGCTGGAGAC 3475 TCTCCAGCCAGGCTTTGGCGCCAAAGCCTGGCTGGAGA 3476 CTCCAGCCAGGCTTTGGCA TGCCAAAGCCTGGCTGGAG 3477TCCAGCCAGGCTTTGGCAG CTGCCAAAGCCTGGCTGGA 3478 CCAGCCAGGCTTTGGCAGATCTGCCAAAGCCTGGCTGG 3479 CAGCCAGGCTTTGGCAGAG CTCTGCCAAAGCCTGGCTG 3480AGCCAGGCTTTGGCAGAGC GCTCTGCCAAAGCCTGGCT 3481 GCCAGGCTTTGGCAGAGCTAGCTCTGCCAAAGCCTGGC 3482 CCAGGCTTTGGCAGAGCTG CAGCTCTGCCAAAGCCTGG 3483CAGGCTTTGGCAGAGCTGA TCAGCTCTGCCAAAGCCTG 3484 AGGCTTTGGCAGAGCTGAGCTCAGCTCTGCCAAAGCCT 3485 GGCTTTGGCAGAGCTGAGC GCTCAGCTCTGCCAAAGCC 3486GCTTTGGCAGAGCTGAGCA TGCTCAGCTCTGCCAAAGC 3487 CTTTGGCAGAGCTGAGCACGTGCTCAGCTCTGCCAAAG 3488 TTTGGCAGAGCTGAGCACT AGTGCTCAGCTCTGCCAAA 3489TTGGCAGAGCTGAGCACTG CAGTGCTCAGCTCTGCCAA 3490 TGGCAGAGCTGAGCACTGCGCAGTGCTCAGCTCTGCCA 3491 GGCAGAGCTGAGCACTGCA TGCAGTGCTCAGCTCTGCC 3492GCAGAGCTGAGCACTGCAA TTGCAGTGCTCAGCTCTGC 3493 CAGAGCTGAGCACTGCAATATTGCAGTGCTCAGCTCTG 3494 AGAGCTGAGCACTGCAATG CATTGCAGTGCTCAGCTCT 3495GAGCTGAGCACTGCAATGC GCATTGCAGTGCTCAGCTC 3496 AGCTGAGCACTGCAATGCATGCATTGCAGTGCTCAGCT 3497 GCTGAGCACTGCAATGCAC GTGCATTGCAGTGCTCAGC 3498CTGAGCACTGCAATGCACC GGTGCATTGCAGTGCTCAG 3499 TGAGCACTGCAATGCACCATGGTGCATTGCAGTGCTCA 3500 GAGCACTGCAATGCACCAG CTGGTGCATTGCAGTGCTC 3501AGCACTGCAATGCACCAGG CCTGGTGCATTGCAGTGCT 3502 GCACTGCAATGCACCAGGTACCTGGTGCATTGCAGTGC 3503 CACTGCAATGCACCAGGTC GACCTGGTGCATTGCAGTG 3504ACTGCAATGCACCAGGTCT AGACCTGGTGCATTGCAGT 3505 CTGCAATGCACCAGGTCTGCAGACCTGGTGCATTGCAG 3506 TGCAATGCACCAGGTCTGG CCAGACCTGGTGCATTGCA 3507GCAATGCACCAGGTCTGGG CCCAGACCTGGTGCATTGC 3508 CAATGCACCAGGTCTGGGTACCCAGACCTGGTGCATTG 3509 AATGCACCAGGTCTGGGTC GACCCAGACCTGGTGCATT 3510ATGCACCAGGTCTGGGTCA TGACCCAGACCTGGTGCAT 3511 TGCACCAGGTCTGGGTCAATTGACCCAGACCTGGTGCA 3512 GCACCAGGTCTGGGTCAAG CTTGACCCAGACCTGGTGC 3513CACCAGGTCTGGGTCAAGT ACTTGACCCAGACCTGGTG 3514 ACCAGGTCTGGGTCAAGTTAACTTGACCCAGACCTGGT 3515 CCAGGTCTGGGTCAAGTTT AAACTTGACCCAGACCTGG 3516CAGGTCTGGGTCAAGTTTG CAAACTTGACCCAGACCTG 3517 AGGTCTGGGTCAAGTTTGATCAAACTTGACCCAGACCT 3518 GGTCTGGGTCAAGTTTGAT ATCAAACTTGACCCAGACC 3519GTCTGGGTCAAGTTTGATA TATCAAACTTGACCCAGAC 3520 TCTGGGTCAAGTTTGATATATATCAAACTTGACCCAGA 3521 CTGGGTCAAGTTTGATATC GATATCAAACTTGACCCAG 3522TGGGTCAAGTTTGATATCC GGATATCAAACTTGACCCA 3523 GGGTCAAGTTTGATATCCGCGGATATCAAACTTGACCC 3524 GGTCAAGTTTGATATCCGG CCGGATATCAAACTTGACC 3525GTCAAGTTTGATATCCGGG CCCGGATATCAAACTTGAC 3526 TCAAGTTTGATATCCGGGGCCCCGGATATCAAACTTGA 3527 CAAGTTTGATATCCGGGGG CCCCCGGATATCAAACTTG 3528AAGTTTGATATCCGGGGGC GCCCCCGGATATCAAACTT 3529 AGTTTGATATCCGGGGGCATGCCCCCGGATATCAAACT 3530 GTTTGATATCCGGGGGCAC GTGCCCCCGGATATCAAAC 3531TTTGATATCCGGGGGCACT AGTGCCCCCGGATATCAAA 3532 TTGATATCCGGGGGCACTGCAGTGCCCCCGGATATCAA 3533 TGATATCCGGGGGCACTGC GCAGTGCCCCCGGATATCA 3534GATATCCGGGGGCACTGCC GGCAGTGCCCCCGGATATC 3535 ATATCCGGGGGCACTGCCCGGGCAGTGCCCCCGGATAT 3536 TATCCGGGGGCACTGCCCC GGGGCAGTGCCCCCGGATA 3537ATCCGGGGGCACTGCCCCT AGGGGCAGTGCCCCCGGAT 3538 TCCGGGGGCACTGCCCCTGCAGGGGCAGTGCCCCCGGA 3539 CCGGGGGCACTGCCCCTGC GCAGGGGCAGTGCCCCCGG 3540CGGGGGCACTGCCCCTGCC GGCAGGGGCAGTGCCCCCG 3541 GGGGGCACTGCCCCTGCCATGGCAGGGGCAGTGCCCCC 3542 GGGGCACTGCCCCTGCCAA TTGGCAGGGGCAGTGCCCC 3543GGGCACTGCCCCTGCCAAG CTTGGCAGGGGCAGTGCCC 3544 GGCACTGCCCCTGCCAAGCGCTTGGCAGGGGCAGTGCC 3545 GCACTGCCCCTGCCAAGCT AGCTTGGCAGGGGCAGTGC 3546CACTGCCCCTGCCAAGCTG CAGCTTGGCAGGGGCAGTG 3547 ACTGCCCCTGCCAAGCTGATCAGCTTGGCAGGGGCAGT 3548 CTGCCCCTGCCAAGCTGAT ATCAGCTTGGCAGGGGCAG 3549TGCCCCTGCCAAGCTGATG CATCAGCTTGGCAGGGGCA 3550 GCCCCTGCCAAGCTGATGCGCATCAGCTTGGCAGGGGC 3551 CCCCTGCCAAGCTGATGCC GGCATCAGCTTGGCAGGGG 3552CCCTGCCAAGCTGATGCCC GGGCATCAGCTTGGCAGGG 3553 CCTGCCAAGCTGATGCCCGCGGGCATCAGCTTGGCAGG 3554 CTGCCAAGCTGATGCCCGG CCGGGCATCAGCTTGGCAG 3555TGCCAAGCTGATGCCCGGG CCCGGGCATCAGCTTGGCA 3556 GCCAAGCTGATGCCCGGGTACCCGGGCATCAGCTTGGC 3557 CCAAGCTGATGCCCGGGTA TACCCGGGCATCAGCTTGG 3558CAAGCTGATGCCCGGGTAT ATACCCGGGCATCAGCTTG 3559 AAGCTGATGCCCGGGTATGCATACCCGGGCATCAGCTT 3560 AGCTGATGCCCGGGTATGG CCATACCCGGGCATCAGCT 3561GCTGATGCCCGGGTATGGG CCCATACCCGGGCATCAGC 3562 CTGATGCCCGGGTATGGGCGCCCATACCCGGGCATCAG 3563 TGATGCCCGGGTATGGGCC GGCCCATACCCGGGCATCA 3564GATGCCCGGGTATGGGCCC GGGCCCATACCCGGGCATC 3565 ATGCCCGGGTATGGGCCCCGGGGCCCATACCCGGGCAT 3566 TGCCCGGGTATGGGCCCCC GGGGGCCCATACCCGGGCA 3567GCCCGGGTATGGGCCCCCG CGGGGGCCCATACCCGGGC 3568 CCCGGGTATGGGCCCCCGGCCGGGGGCCCATACCCGGG 3569 CCGGGTATGGGCCCCCGGG CCCGGGGGCCCATACCCGG 3570CGGGTATGGGCCCCCGGGG CCCCGGGGGCCCATACCCG 3571 GGGTATGGGCCCCCGGGGATCCCCGGGGGCCCATACCC 3572 GGTATGGGCCCCCGGGGAT ATCCCCGGGGGCCCATACC 3573GTATGGGCCCCCGGGGATG CATCCCCGGGGGCCCATAC 3574 TATGGGCCCCCGGGGATGCGCATCCCCGGGGGCCCATA 3575 ATGGGCCCCCGGGGATGCA TGCATCCCCGGGGGCCCAT 3576TGGGCCCCCGGGGATGCAG CTGCATCCCCGGGGGCCCA 3577 GGGCCCCCGGGGATGCAGGCCTGCATCCCCGGGGGCCC 3578 GGCCCCCGGGGATGCAGGC GCCTGCATCCCCGGGGGCC 3579GCCCCCGGGGATGCAGGCC GGCCTGCATCCCCGGGGGC 3580 CCCCCGGGGATGCAGGCCATGGCCTGCATCCCCGGGGG 3581 CCCCGGGGATGCAGGCCAG CTGGCCTGCATCCCCGGGG 3582CCCGGGGATGCAGGCCAGC GCTGGCCTGCATCCCCGGG 3583 CCGGGGATGCAGGCCAGCATGCTGGCCTGCATCCCCGG 3584 CGGGGATGCAGGCCAGCAG CTGCTGGCCTGCATCCCCG 3585GGGGATGCAGGCCAGCAGA TCTGCTGGCCTGCATCCCC 3586 GGGATGCAGGCCAGCAGAATTCTGCTGGCCTGCATCCC 3587 GGATGCAGGCCAGCAGAAG CTTCTGCTGGCCTGCATCC 3588GATGCAGGCCAGCAGAAGG CCTTCTGCTGGCCTGCATC 3589 ATGCAGGCCAGCAGAAGGATCCTTCTGCTGGCCTGCAT 3590 TGCAGGCCAGCAGAAGGAA TTCCTTCTGCTGGCCTGCA 3591GCAGGCCAGCAGAAGGAAT ATTCCTTCTGCTGGCCTGC 3592 CAGGCCAGCAGAAGGAATCGATTCCTTCTGCTGGCCTG 3593 AGGCCAGCAGAAGGAATCA TGATTCCTTCTGCTGGCCT 3594GGCCAGCAGAAGGAATCAA TTGATTCCTTCTGCTGGCC 3595 GCCAGCAGAAGGAATCAACGTTGATTCCTTCTGCTGGC 3596 CCAGCAGAAGGAATCAACA TGTTGATTCCTTCTGCTGG 3597CAGCAGAAGGAATCAACAC GTGTTGATTCCTTCTGCTG 3598 AGCAGAAGGAATCAACACATGTGTTGATTCCTTCTGCT 3599 GCAGAAGGAATCAACACAG CTGTGTTGATTCCTTCTGC 3600CAGAAGGAATCAACACAGA TCTGTGTTGATTCCTTCTG 3601 AGAAGGAATCAACACAGAATTCTGTGTTGATTCCTTCT 3602 GAAGGAATCAACACAGAAA TTTCTGTGTTGATTCCTTC 3603AAGGAATCAACACAGAAAA TTTTCTGTGTTGATTCCTT 3604 AGGAATCAACACAGAAAACGTTTTCTGTGTTGATTCCT 3605 GGAATCAACACAGAAAACG CGTTTTCTGTGTTGATTCC 3606GAATCAACACAGAAAACGC GCGTTTTCTGTGTTGATTC 3607 AATCAACACAGAAAACGCCGGCGTTTTCTGTGTTGATT 3608 ATCAACACAGAAAACGCCC GGGCGTTTTCTGTGTTGAT 3609TCAACACAGAAAACGCCCC GGGGCGTTTTCTGTGTTGA 3610 CAACACAGAAAACGCCCCCGGGGGCGTTTTCTGTGTTG 3611 AACACAGAAAACGCCCCCA TGGGGGCGTTTTCTGTGTT 3612ACACAGAAAACGCCCCCAA TTGGGGGCGTTTTCTGTGT 3613 CACAGAAAACGCCCCCAACGTTGGGGGCGTTTTCTGTG 3614 ACAGAAAACGCCCCCAACT AGTTGGGGGCGTTTTCTGT 3615CAGAAAACGCCCCCAACTC GAGTTGGGGGCGTTTTCTG 3616 AGAAAACGCCCCCAACTCCGGAGTTGGGGGCGTTTTCT 3617 GAAAACGCCCCCAACTCCA TGGAGTTGGGGGCGTTTTC 3618AAAACGCCCCCAACTCCAC GTGGAGTTGGGGGCGTTTT 3619 AAACGCCCCCAACTCCACATGTGGAGTTGGGGGCGTTT 3620 AACGCCCCCAACTCCACAA TTGTGGAGTTGGGGGCGTT 3621ACGCCCCCAACTCCACAAC GTTGTGGAGTTGGGGGCGT 3622 CGCCCCCAACTCCACAACCGGTTGTGGAGTTGGGGGCG 3623 GCCCCCAACTCCACAACCT AGGTTGTGGAGTTGGGGGC 3624CCCCCAACTCCACAACCTT AAGGTTGTGGAGTTGGGGG 3625 CCCCAACTCCACAACCTTCGAAGGTTGTGGAGTTGGGG 3626 CCCAACTCCACAACCTTCC GGAAGGTTGTGGAGTTGGG 3627CCAACTCCACAACCTTCCT AGGAAGGTTGTGGAGTTGG 3628 CAACTCCACAACCTTCCTGCAGGAAGGTTGTGGAGTTG 3629 AACTCCACAACCTTCCTGC GCAGGAAGGTTGTGGAGTT 3630ACTCCACAACCTTCCTGCA TGCAGGAAGGTTGTGGAGT 3631 CTCCACAACCTTCCTGCAATTGCAGGAAGGTTGTGGAG 3632 TCCACAACCTTCCTGCAAT ATTGCAGGAAGGTTGTGGA 3633CCACAACCTTCCTGCAATG CATTGCAGGAAGGTTGTGG 3634 CACAACCTTCCTGCAATGGCCATTGCAGGAAGGTTGTG 3635 ACAACCTTCCTGCAATGGC GCCATTGCAGGAAGGTTGT 3636CAACCTTCCTGCAATGGCG CGCCATTGCAGGAAGGTTG 3637 AACCTTCCTGCAATGGCGATCGCCATTGCAGGAAGGTT 3638 ACCTTCCTGCAATGGCGAC GTCGCCATTGCAGGAAGGT 3639CCTTCCTGCAATGGCGACA TGTCGCCATTGCAGGAAGG 3640 CTTCCTGCAATGGCGACACGTGTCGCCATTGCAGGAAG 3641 TTCCTGCAATGGCGACACC GGTGTCGCCATTGCAGGAA 3642TCCTGCAATGGCGACACCC GGGTGTCGCCATTGCAGGA 3643 CCTGCAATGGCGACACCCATGGGTGTCGCCATTGCAGG 3644 CTGCAATGGCGACACCCAC GTGGGTGTCGCCATTGCAG 3645TGCAATGGCGACACCCACA TGTGGGTGTCGCCATTGCA 3646 GCAATGGCGACACCCACAGCTGTGGGTGTCGCCATTGC 3647 CAATGGCGACACCCACAGG CCTGTGGGTGTCGCCATTG 3648AATGGCGACACCCACAGGA TCCTGTGGGTGTCGCCATT 3649 ATGGCGACACCCACAGGACGTCCTGTGGGTGTCGCCAT 3650 TGGCGACACCCACAGGACC GGTCCTGTGGGTGTCGCCA 3651GGCGACACCCACAGGACCA TGGTCCTGTGGGTGTCGCC 3652 GCGACACCCACAGGACCAATTGGTCCTGTGGGTGTCGC 3653 CGACACCCACAGGACCAAG CTTGGTCCTGTGGGTGTCG 3654GACACCCACAGGACCAAGA TCTTGGTCCTGTGGGTGTC 3655 ACACCCACAGGACCAAGAGCTCTTGGTCCTGTGGGTGT 3656 CACCCACAGGACCAAGAGC GCTCTTGGTCCTGTGGGTG 3657ACCCACAGGACCAAGAGCA TGCTCTTGGTCCTGTGGGT 3658 CCCACAGGACCAAGAGCATATGCTCTTGGTCCTGTGGG 3659 CCACAGGACCAAGAGCATC GATGCTCTTGGTCCTGTGG 3660CACAGGACCAAGAGCATCA TGATGCTCTTGGTCCTGTG 3661 ACAGGACCAAGAGCATCAATTGATGCTCTTGGTCCTGT 3662 CAGGACCAAGAGCATCAAA TTTGATGCTCTTGGTCCTG 3663AGGACCAAGAGCATCAAAG CTTTGATGCTCTTGGTCCT 3664 GGACCAAGAGCATCAAAGATCTTTGATGCTCTTGGTCC 3665 GACCAAGAGCATCAAAGAG CTCTTTGATGCTCTTGGTC 3666ACCAAGAGCATCAAAGAGG CCTCTTTGATGCTCTTGGT 3667 CCAAGAGCATCAAAGAGGATCCTCTTTGATGCTCTTGG 3668 CAAGAGCATCAAAGAGGAG CTCCTCTTTGATGCTCTTG 3669AAGAGCATCAAAGAGGAGA TCTCCTCTTTGATGCTCTT 3670 AGAGCATCAAAGAGGAGACGTCTCCTCTTTGATGCTCT 3671 GAGCATCAAAGAGGAGACC GGTCTCCTCTTTGATGCTC 3672AGCATCAAAGAGGAGACCC GGGTCTCCTCTTTGATGCT 3673 GCATCAAAGAGGAGACCCCGGGGTCTCCTCTTTGATGC 3674 CATCAAAGAGGAGACCCCC GGGGGTCTCCTCTTTGATG 3675ATCAAAGAGGAGACCCCCG CGGGGGTCTCCTCTTTGAT 3676 TCAAAGAGGAGACCCCCGATCGGGGGTCTCCTCTTTGA 3677 CAAAGAGGAGACCCCCGAT ATCGGGGGTCTCCTCTTTG 3678AAAGAGGAGACCCCCGATT AATCGGGGGTCTCCTCTTT 3679 AAGAGGAGACCCCCGATTCGAATCGGGGGTCTCCTCTT 3680 AGAGGAGACCCCCGATTCC GGAATCGGGGGTCTCCTCT 3681GAGGAGACCCCCGATTCCG CGGAATCGGGGGTCTCCTC 3682 AGGAGACCCCCGATTCCGCGCGGAATCGGGGGTCTCCT 3683 GGAGACCCCCGATTCCGCT AGCGGAATCGGGGGTCTCC 3684GAGACCCCCGATTCCGCTG CAGCGGAATCGGGGGTCTC 3685 AGACCCCCGATTCCGCTGATCAGCGGAATCGGGGGTCT 3686 GACCCCCGATTCCGCTGAG CTCAGCGGAATCGGGGGTC 3687ACCCCCGATTCCGCTGAGA TCTCAGCGGAATCGGGGGT 3688 CCCCCGATTCCGCTGAGACGTCTCAGCGGAATCGGGGG 3689 CCCCGATTCCGCTGAGACC GGTCTCAGCGGAATCGGGG 3690CCCGATTCCGCTGAGACCC GGGTCTCAGCGGAATCGGG 3691 CCGATTCCGCTGAGACCCCGGGGTCTCAGCGGAATCGG 3692 CGATTCCGCTGAGACCCCA TGGGGTCTCAGCGGAATCG 3693GATTCCGCTGAGACCCCAG CTGGGGTCTCAGCGGAATC 3694 ATTCCGCTGAGACCCCAGCGCTGGGGTCTCAGCGGAAT 3695 TTCCGCTGAGACCCCAGCA TGCTGGGGTCTCAGCGGAA 3696TCCGCTGAGACCCCAGCAG CTGCTGGGGTCTCAGCGGA 3697 CCGCTGAGACCCCAGCAGATCTGCTGGGGTCTCAGCGG 3698 CGCTGAGACCCCAGCAGAG CTCTGCTGGGGTCTCAGCG 3699GCTGAGACCCCAGCAGAGG CCTCTGCTGGGGTCTCAGC 3700 CTGAGACCCCAGCAGAGGATCCTCTGCTGGGGTCTCAG 3701 TGAGACCCCAGCAGAGGAC GTCCTCTGCTGGGGTCTCA 3702GAGACCCCAGCAGAGGACC GGTCCTCTGCTGGGGTCTC 3703 AGACCCCAGCAGAGGACCGCGGTCCTCTGCTGGGGTCT 3704 GACCCCAGCAGAGGACCGT ACGGTCCTCTGCTGGGGTC 3705ACCCCAGCAGAGGACCGTG CACGGTCCTCTGCTGGGGT 3706 CCCCAGCAGAGGACCGTGCGCACGGTCCTCTGCTGGGG 3707 CCCAGCAGAGGACCGTGCT AGCACGGTCCTCTGCTGGG 3708CCAGCAGAGGACCGTGCTG CAGCACGGTCCTCTGCTGG 3709 CAGCAGAGGACCGTGCTGGCCAGCACGGTCCTCTGCTG 3710 AGCAGAGGACCGTGCTGGC GCCAGCACGGTCCTCTGCT 3711GCAGAGGACCGTGCTGGCC GGCCAGCACGGTCCTCTGC 3712 CAGAGGACCGTGCTGGCCGCGGCCAGCACGGTCCTCTG 3713 AGAGGACCGTGCTGGCCGA TCGGCCAGCACGGTCCTCT 3714GAGGACCGTGCTGGCCGAG CTCGGCCAGCACGGTCCTC 3715 AGGACCGTGCTGGCCGAGGCCTCGGCCAGCACGGTCCT 3716 GGACCGTGCTGGCCGAGGG CCCTCGGCCAGCACGGTCC 3717GACCGTGCTGGCCGAGGGC GCCCTCGGCCAGCACGGTC 3718 ACCGTGCTGGCCGAGGGCCGGCCCTCGGCCAGCACGGT 3719 CCGTGCTGGCCGAGGGCCC GGGCCCTCGGCCAGCACGG 3720CGTGCTGGCCGAGGGCCCC GGGGCCCTCGGCCAGCACG 3721 GTGCTGGCCGAGGGCCCCTAGGGGCCCTCGGCCAGCAC 3722 TGCTGGCCGAGGGCCCCTG CAGGGGCCCTCGGCCAGCA 3723GCTGGCCGAGGGCCCCTGC GCAGGGGCCCTCGGCCAGC 3724 CTGGCCGAGGGCCCCTGCCGGCAGGGGCCCTCGGCCAG 3725 TGGCCGAGGGCCCCTGCCT AGGCAGGGGCCCTCGGCCA 3726GGCCGAGGGCCCCTGCCTT AAGGCAGGGGCCCTCGGCC 3727 GCCGAGGGCCCCTGCCTTGCAAGGCAGGGGCCCTCGGC 3728 CCGAGGGCCCCTGCCTTGT ACAAGGCAGGGGCCCTCGG 3729CGAGGGCCCCTGCCTTGTC GACAAGGCAGGGGCCCTCG 3730 GAGGGCCCCTGCCTTGTCCGGACAAGGCAGGGGCCCTC 3731 AGGGCCCCTGCCTTGTCCT AGGACAAGGCAGGGGCCCT 3732GGGCCCCTGCCTTGTCCTT AAGGACAAGGCAGGGGCCC 3733 GGCCCCTGCCTTGTCCTTCGAAGGACAAGGCAGGGGCC 3734 GCCCCTGCCTTGTCCTTCT AGAAGGACAAGGCAGGGGC 3735CCCCTGCCTTGTCCTTCTC GAGAAGGACAAGGCAGGGG 3736 CCCTGCCTTGTCCTTCTCTAGAGAAGGACAAGGCAGGG 3737 CCTGCCTTGTCCTTCTCTC GAGAGAAGGACAAGGCAGG 3738CTGCCTTGTCCTTCTCTCT AGAGAGAAGGACAAGGCAG 3739 TGCCTTGTCCTTCTCTCTGCAGAGAGAAGGACAAGGCA 3740 GCCTTGTCCTTCTCTCTGC GCAGAGAGAAGGACAAGGC 3741CCTTGTCCTTCTCTCTGCG CGCAGAGAGAAGGACAAGG 3742 CTTGTCCTTCTCTCTGCGATCGCAGAGAGAAGGACAAG 3743 TTGTCCTTCTCTCTGCGAA TTCGCAGAGAGAAGGACAA 3744TGTCCTTCTCTCTGCGAAC GTTCGCAGAGAGAAGGACA 3745 GTCCTTCTCTCTGCGAACTAGTTCGCAGAGAGAAGGAC 3746 TCCTTCTCTCTGCGAACTG CAGTTCGCAGAGAGAAGGA 3747CCTTCTCTCTGCGAACTGC GCAGTTCGCAGAGAGAAGG 3748 CTTCTCTCTGCGAACTGCTAGCAGTTCGCAGAGAGAAG 3749 TTCTCTCTGCGAACTGCTG CAGCAGTTCGCAGAGAGAA 3750TCTCTCTGCGAACTGCTGG CCAGCAGTTCGCAGAGAGA 3751 CTCTCTGCGAACTGCTGGCGCCAGCAGTTCGCAGAGAG 3752 TCTCTGCGAACTGCTGGCT AGCCAGCAGTTCGCAGAGA 3753CTCTGCGAACTGCTGGCTT AAGCCAGCAGTTCGCAGAG 3754 TCTGCGAACTGCTGGCTTCGAAGCCAGCAGTTCGCAGA 3755 CTGCGAACTGCTGGCTTCT AGAAGCCAGCAGTTCGCAG 3756TGCGAACTGCTGGCTTCTA TAGAAGCCAGCAGTTCGCA 3757 GCGAACTGCTGGCTTCTACGTAGAAGCCAGCAGTTCGC 3758 CGAACTGCTGGCTTCTACC GGTAGAAGCCAGCAGTTCG 3759GAACTGCTGGCTTCTACCG CGGTAGAAGCCAGCAGTTC 3760 AACTGCTGGCTTCTACCGCGCGGTAGAAGCCAGCAGTT 3761 ACTGCTGGCTTCTACCGCG CGCGGTAGAAGCCAGCAGT 3762CTGCTGGCTTCTACCGCGG CCGCGGTAGAAGCCAGCAG 3763 TGCTGGCTTCTACCGCGGTACCGCGGTAGAAGCCAGCA 3764 GCTGGCTTCTACCGCGGTC GACCGCGGTAGAAGCCAGC 3765CTGGCTTCTACCGCGGTCA TGACCGCGGTAGAAGCCAG 3766 TGGCTTCTACCGCGGTCAATTGACCGCGGTAGAAGCCA 3767 GGCTTCTACCGCGGTCAAA TTTGACCGCGGTAGAAGCC 3768GCTTCTACCGCGGTCAAAC GTTTGACCGCGGTAGAAGC 3769 CTTCTACCGCGGTCAAACTAGTTTGACCGCGGTAGAAG 3770 TTCTACCGCGGTCAAACTC GAGTTTGACCGCGGTAGAA 3771TCTACCGCGGTCAAACTCT AGAGTTTGACCGCGGTAGA 3772 CTACCGCGGTCAAACTCTGCAGAGTTTGACCGCGGTAG 3773 TACCGCGGTCAAACTCTGC GCAGAGTTTGACCGCGGTA 3774ACCGCGGTCAAACTCTGCT AGCAGAGTTTGACCGCGGT 3775 CCGCGGTCAAACTCTGCTTAAGCAGAGTTTGACCGCGG 3776 CGCGGTCAAACTCTGCTTG CAAGCAGAGTTTGACCGCG 3777GCGGTCAAACTCTGCTTGG CCAAGCAGAGTTTGACCGC 3778 CGGTCAAACTCTGCTTGGGCCCAAGCAGAGTTTGACCG 3779 GGTCAAACTCTGCTTGGGC GCCCAAGCAGAGTTTGACC 3780GTCAAACTCTGCTTGGGCC GGCCCAAGCAGAGTTTGAC 3781 TCAAACTCTGCTTGGGCCATGGCCCAAGCAGAGTTTGA 3782 CAAACTCTGCTTGGGCCAT ATGGCCCAAGCAGAGTTTG 3783AAACTCTGCTTGGGCCATG CATGGCCCAAGCAGAGTTT 3784 AACTCTGCTTGGGCCATGATCATGGCCCAAGCAGAGTT 3785 ACTCTGCTTGGGCCATGAG CTCATGGCCCAAGCAGAGT 3786CTCTGCTTGGGCCATGAGC GCTCATGGCCCAAGCAGAG 3787 TCTGCTTGGGCCATGAGCGCGCTCATGGCCCAAGCAGA 3788 CTGCTTGGGCCATGAGCGA TCGCTCATGGCCCAAGCAG 3789TGCTTGGGCCATGAGCGAA TTCGCTCATGGCCCAAGCA 3790 GCTTGGGCCATGAGCGAATATTCGCTCATGGCCCAAGC 3791 CTTGGGCCATGAGCGAATA TATTCGCTCATGGCCCAAG 3792TTGGGCCATGAGCGAATAC GTATTCGCTCATGGCCCAA 3793 TGGGCCATGAGCGAATACATGTATTCGCTCATGGCCCA 3794 GGGCCATGAGCGAATACAC GTGTATTCGCTCATGGCCC 3795GGCCATGAGCGAATACACA TGTGTATTCGCTCATGGCC 3796 GCCATGAGCGAATACACATATGTGTATTCGCTCATGGC 3797 CCATGAGCGAATACACATG CATGTGTATTCGCTCATGG 3798CATGAGCGAATACACATGG CCATGTGTATTCGCTCATG 3799 ATGAGCGAATACACATGGCGCCATGTGTATTCGCTCAT 3800 TGAGCGAATACACATGGCC GGCCATGTGTATTCGCTCA 3801GAGCGAATACACATGGCCT AGGCCATGTGTATTCGCTC 3802 AGCGAATACACATGGCCTTAAGGCCATGTGTATTCGCT 3803 GCGAATACACATGGCCTTC GAAGGCCATGTGTATTCGC 3804CGAATACACATGGCCTTCG CGAAGGCCATGTGTATTCG 3805 GAATACACATGGCCTTCGCGCGAAGGCCATGTGTATTC 3806 AATACACATGGCCTTCGCC GGCGAAGGCCATGTGTATT 3807ATACACATGGCCTTCGCCC GGGCGAAGGCCATGTGTAT 3808 TACACATGGCCTTCGCCCCGGGGCGAAGGCCATGTGTA 3809 ACACATGGCCTTCGCCCCC GGGGGCGAAGGCCATGTGT 3810CACATGGCCTTCGCCCCCG CGGGGGCGAAGGCCATGTG 3811 ACATGGCCTTCGCCCCCGTACGGGGGCGAAGGCCATGT 3812 CATGGCCTTCGCCCCCGTC GACGGGGGCGAAGGCCATG 3813ATGGCCTTCGCCCCCGTCA TGACGGGGGCGAAGGCCAT 3814 TGGCCTTCGCCCCCGTCACGTGACGGGGGCGAAGGCCA 3815 GGCCTTCGCCCCCGTCACT AGTGACGGGGGCGAAGGCC 3816GCCTTCGCCCCCGTCACTC GAGTGACGGGGGCGAAGGC 3817 CCTTCGCCCCCGTCACTCCGGAGTGACGGGGGCGAAGG 3818 CTTCGCCCCCGTCACTCCG CGGAGTGACGGGGGCGAAG 3819TTCGCCCCCGTCACTCCGG CCGGAGTGACGGGGGCGAA 3820 TCGCCCCCGTCACTCCGGCGCCGGAGTGACGGGGGCGA 3821 CGCCCCCGTCACTCCGGCC GGCCGGAGTGACGGGGGCG 3822GCCCCCGTCACTCCGGCCC GGGCCGGAGTGACGGGGGC 3823 CCCCCGTCACTCCGGCCCTAGGGCCGGAGTGACGGGGG 3824 CCCCGTCACTCCGGCCCTG CAGGGCCGGAGTGACGGGG 3825CCCGTCACTCCGGCCCTGC GCAGGGCCGGAGTGACGGG 3826 CCGTCACTCCGGCCCTGCCGGCAGGGCCGGAGTGACGG 3827 CGTCACTCCGGCCCTGCCC GGGCAGGGCCGGAGTGACG 3828GTCACTCCGGCCCTGCCCA TGGGCAGGGCCGGAGTGAC 3829 TCACTCCGGCCCTGCCCAGCTGGGCAGGGCCGGAGTGA 3830 CACTCCGGCCCTGCCCAGT ACTGGGCAGGGCCGGAGTG 3831ACTCCGGCCCTGCCCAGTG CACTGGGCAGGGCCGGAGT 3832 CTCCGGCCCTGCCCAGTGATCACTGGGCAGGGCCGGAG 3833 TCCGGCCCTGCCCAGTGAT ATCACTGGGCAGGGCCGGA 3834CCGGCCCTGCCCAGTGATG CATCACTGGGCAGGGCCGG 3835 CGGCCCTGCCCAGTGATGATCATCACTGGGCAGGGCCG 3836 GGCCCTGCCCAGTGATGAC GTCATCACTGGGCAGGGCC 3837GCCCTGCCCAGTGATGACC GGTCATCACTGGGCAGGGC 3838 CCCTGCCCAGTGATGACCGCGGTCATCACTGGGCAGGG 3839 CCTGCCCAGTGATGACCGC GCGGTCATCACTGGGCAGG 3840CTGCCCAGTGATGACCGCA TGCGGTCATCACTGGGCAG 3841 TGCCCAGTGATGACCGCATATGCGGTCATCACTGGGCA 3842 GCCCAGTGATGACCGCATC GATGCGGTCATCACTGGGC 3843CCCAGTGATGACCGCATCA TGATGCGGTCATCACTGGG 3844 CCAGTGATGACCGCATCACGTGATGCGGTCATCACTGG 3845 CAGTGATGACCGCATCACC GGTGATGCGGTCATCACTG 3846AGTGATGACCGCATCACCA TGGTGATGCGGTCATCACT 3847 GTGATGACCGCATCACCAATTGGTGATGCGGTCATCAC 3848 TGATGACCGCATCACCAAC GTTGGTGATGCGGTCATCA 3849GATGACCGCATCACCAACA TGTTGGTGATGCGGTCATC 3850 ATGACCGCATCACCAACATATGTTGGTGATGCGGTCAT 3851 TGACCGCATCACCAACATC GATGTTGGTGATGCGGTCA 3852GACCGCATCACCAACATCC GGATGTTGGTGATGCGGTC 3853 ACCGCATCACCAACATCCTAGGATGTTGGTGATGCGGT 3854 CCGCATCACCAACATCCTG CAGGATGTTGGTGATGCGG 3855CGCATCACCAACATCCTGG CCAGGATGTTGGTGATGCG 3856 GCATCACCAACATCCTGGATCCAGGATGTTGGTGATGC 3857 CATCACCAACATCCTGGAC GTCCAGGATGTTGGTGATG 3858ATCACCAACATCCTGGACA TGTCCAGGATGTTGGTGAT 3859 TCACCAACATCCTGGACAGCTGTCCAGGATGTTGGTGA 3860 CACCAACATCCTGGACAGC GCTGTCCAGGATGTTGGTG 3861ACCAACATCCTGGACAGCA TGCTGTCCAGGATGTTGGT 3862 CCAACATCCTGGACAGCATATGCTGTCCAGGATGTTGG 3863 CAACATCCTGGACAGCATT AATGCTGTCCAGGATGTTG 3864AACATCCTGGACAGCATTA TAATGCTGTCCAGGATGTT 3865 ACATCCTGGACAGCATTATATAATGCTGTCCAGGATGT 3866 CATCCTGGACAGCATTATC GATAATGCTGTCCAGGATG 3867ATCCTGGACAGCATTATCG CGATAATGCTGTCCAGGAT 3868 TCCTGGACAGCATTATCGCGCGATAATGCTGTCCAGGA 3869 CCTGGACAGCATTATCGCA TGCGATAATGCTGTCCAGG 3870CTGGACAGCATTATCGCAC GTGCGATAATGCTGTCCAG 3871 TGGACAGCATTATCGCACATGTGCGATAATGCTGTCCA 3872 GGACAGCATTATCGCACAG CTGTGCGATAATGCTGTCC 3873GACAGCATTATCGCACAGG CCTGTGCGATAATGCTGTC 3874 ACAGCATTATCGCACAGGTACCTGTGCGATAATGCTGT 3875 CAGCATTATCGCACAGGTG CACCTGTGCGATAATGCTG 3876AGCATTATCGCACAGGTGG CCACCTGTGCGATAATGCT 3877 GCATTATCGCACAGGTGGTACCACCTGTGCGATAATGC 3878 CATTATCGCACAGGTGGTG CACCACCTGTGCGATAATG 3879ATTATCGCACAGGTGGTGG CCACCACCTGTGCGATAAT 3880 TTATCGCACAGGTGGTGGATCCACCACCTGTGCGATAA 3881 TATCGCACAGGTGGTGGAA TTCCACCACCTGTGCGATA 3882ATCGCACAGGTGGTGGAAC GTTCCACCACCTGTGCGAT 3883 TCGCACAGGTGGTGGAACGCGTTCCACCACCTGTGCGA 3884 CGCACAGGTGGTGGAACGG CCGTTCCACCACCTGTGCG 3885GCACAGGTGGTGGAACGGA TCCGTTCCACCACCTGTGC 3886 CACAGGTGGTGGAACGGAATTCCGTTCCACCACCTGTG 3887 ACAGGTGGTGGAACGGAAG CTTCCGTTCCACCACCTGT 3888CAGGTGGTGGAACGGAAGA TCTTCCGTTCCACCACCTG 3889 AGGTGGTGGAACGGAAGATATCTTCCGTTCCACCACCT 3890 GGTGGTGGAACGGAAGATC GATCTTCCGTTCCACCACC 3891GTGGTGGAACGGAAGATCC GGATCTTCCGTTCCACCAC 3892 TGGTGGAACGGAAGATCCATGGATCTTCCGTTCCACCA 3893 GGTGGAACGGAAGATCCAG CTGGATCTTCCGTTCCACC 3894GTGGAACGGAAGATCCAGG CCTGGATCTTCCGTTCCAC 3895 TGGAACGGAAGATCCAGGATCCTGGATCTTCCGTTCCA 3896 GGAACGGAAGATCCAGGAG CTCCTGGATCTTCCGTTCC 3897GAACGGAAGATCCAGGAGA TCTCCTGGATCTTCCGTTC 3898 AACGGAAGATCCAGGAGAATTCTCCTGGATCTTCCGTT 3899 ACGGAAGATCCAGGAGAAA TTTCTCCTGGATCTTCCGT 3900CGGAAGATCCAGGAGAAAG CTTTCTCCTGGATCTTCCG 3901 GGAAGATCCAGGAGAAAGCGCTTTCTCCTGGATCTTCC 3902 GAAGATCCAGGAGAAAGCC GGCTTTCTCCTGGATCTTC 3903AAGATCCAGGAGAAAGCCC GGGCTTTCTCCTGGATCTT 3904 AGATCCAGGAGAAAGCCCTAGGGCTTTCTCCTGGATCT 3905 GATCCAGGAGAAAGCCCTG CAGGGCTTTCTCCTGGATC 3906ATCCAGGAGAAAGCCCTGG CCAGGGCTTTCTCCTGGAT 3907 TCCAGGAGAAAGCCCTGGGCCCAGGGCTTTCTCCTGGA 3908 CCAGGAGAAAGCCCTGGGG CCCCAGGGCTTTCTCCTGG 3909CAGGAGAAAGCCCTGGGGC GCCCCAGGGCTTTCTCCTG 3910 AGGAGAAAGCCCTGGGGCCGGCCCCAGGGCTTTCTCCT 3911 GGAGAAAGCCCTGGGGCCG CGGCCCCAGGGCTTTCTCC 3912GAGAAAGCCCTGGGGCCGG CCGGCCCCAGGGCTTTCTC 3913 AGAAAGCCCTGGGGCCGGGCCCGGCCCCAGGGCTTTCT 3914 GAAAGCCCTGGGGCCGGGG CCCCGGCCCCAGGGCTTTC 3915AAAGCCCTGGGGCCGGGGC GCCCCGGCCCCAGGGCTTT 3916 AAGCCCTGGGGCCGGGGCTAGCCCCGGCCCCAGGGCTT 3917 AGCCCTGGGGCCGGGGCTT AAGCCCCGGCCCCAGGGCT 3918GCCCTGGGGCCGGGGCTTC GAAGCCCCGGCCCCAGGGC 3919 CCCTGGGGCCGGGGCTTCGCGAAGCCCCGGCCCCAGGG 3920 CCTGGGGCCGGGGCTTCGA TCGAAGCCCCGGCCCCAGG 3921CTGGGGCCGGGGCTTCGAG CTCGAAGCCCCGGCCCCAG 3922 TGGGGCCGGGGCTTCGAGCGCTCGAAGCCCCGGCCCCA 3923 GGGGCCGGGGCTTCGAGCT AGCTCGAAGCCCCGGCCCC 3924GGGCCGGGGCTTCGAGCTG CAGCTCGAAGCCCCGGCCC 3925 GGCCGGGGCTTCGAGCTGGCCAGCTCGAAGCCCCGGCC 3926 GCCGGGGCTTCGAGCTGGC GCCAGCTCGAAGCCCCGGC 3927CCGGGGCTTCGAGCTGGCC GGCCAGCTCGAAGCCCCGG 3928 CGGGGCTTCGAGCTGGCCCGGGCCAGCTCGAAGCCCCG 3929 GGGGCTTCGAGCTGGCCCG CGGGCCAGCTCGAAGCCCC 3930GGGCTTCGAGCTGGCCCGG CCGGGCCAGCTCGAAGCCC 3931 GGCTTCGAGCTGGCCCGGGCCCGGGCCAGCTCGAAGCC 3932 GCTTCGAGCTGGCCCGGGT ACCCGGGCCAGCTCGAAGC 3933CTTCGAGCTGGCCCGGGTC GACCCGGGCCAGCTCGAAG 3934 TTCGAGCTGGCCCGGGTCTAGACCCGGGCCAGCTCGAA 3935 TCGAGCTGGCCCGGGTCTG CAGACCCGGGCCAGCTCGA 3936CGAGCTGGCCCGGGTCTGC GCAGACCCGGGCCAGCTCG 3937 GAGCTGGCCCGGGTCTGCGCGCAGACCCGGGCCAGCTC 3938 AGCTGGCCCGGGTCTGCGC GCGCAGACCCGGGCCAGCT 3939GCTGGCCCGGGTCTGCGCA TGCGCAGACCCGGGCCAGC 3940 CTGGCCCGGGTCTGCGCAATTGCGCAGACCCGGGCCAG 3941 TGGCCCGGGTCTGCGCAAG CTTGCGCAGACCCGGGCCA 3942GGCCCGGGTCTGCGCAAGG CCTTGCGCAGACCCGGGCC 3943 GCCCGGGTCTGCGCAAGGGCCCTTGCGCAGACCCGGGC 3944 CCCGGGTCTGCGCAAGGGC GCCCTTGCGCAGACCCGGG 3945CCGGGTCTGCGCAAGGGCC GGCCCTTGCGCAGACCCGG 3946 CGGGTCTGCGCAAGGGCCTAGGCCCTTGCGCAGACCCG 3947 GGGTCTGCGCAAGGGCCTG CAGGCCCTTGCGCAGACCC 3948GGTCTGCGCAAGGGCCTGG CCAGGCCCTTGCGCAGACC 3949 GTCTGCGCAAGGGCCTGGGCCCAGGCCCTTGCGCAGAC 3950 TCTGCGCAAGGGCCTGGGC GCCCAGGCCCTTGCGCAGA 3951CTGCGCAAGGGCCTGGGCC GGCCCAGGCCCTTGCGCAG 3952 TGCGCAAGGGCCTGGGCCTAGGCCCAGGCCCTTGCGCA 3953 GCGCAAGGGCCTGGGCCTG CAGGCCCAGGCCCTTGCGC 3954CGCAAGGGCCTGGGCCTGC GCAGGCCCAGGCCCTTGCG 3955 GCAAGGGCCTGGGCCTGCCGGCAGGCCCAGGCCCTTGC 3956 CAAGGGCCTGGGCCTGCCC GGGCAGGCCCAGGCCCTTG 3957AAGGGCCTGGGCCTGCCCC GGGGCAGGCCCAGGCCCTT 3958 AGGGCCTGGGCCTGCCCCTAGGGGCAGGCCCAGGCCCT 3959 GGGCCTGGGCCTGCCCCTC GAGGGGCAGGCCCAGGCCC 3960GGCCTGGGCCTGCCCCTCT AGAGGGGCAGGCCCAGGCC 3961 GCCTGGGCCTGCCCCTCTCGAGAGGGGCAGGCCCAGGC 3962 CCTGGGCCTGCCCCTCTCT AGAGAGGGGCAGGCCCAGG 3963CTGGGCCTGCCCCTCTCTC GAGAGAGGGGCAGGCCCAG 3964 TGGGCCTGCCCCTCTCTCCGGAGAGAGGGGCAGGCCCA 3965 GGGCCTGCCCCTCTCTCCA TGGAGAGAGGGGCAGGCCC 3966GGCCTGCCCCTCTCTCCAG CTGGAGAGAGGGGCAGGCC 3967 GCCTGCCCCTCTCTCCAGTACTGGAGAGAGGGGCAGGC 3968 CCTGCCCCTCTCTCCAGTG CACTGGAGAGAGGGGCAGG 3969CTGCCCCTCTCTCCAGTGC GCACTGGAGAGAGGGGCAG 3970 TGCCCCTCTCTCCAGTGCGCGCACTGGAGAGAGGGGCA 3971 GCCCCTCTCTCCAGTGCGG CCGCACTGGAGAGAGGGGC 3972CCCCTCTCTCCAGTGCGGC GCCGCACTGGAGAGAGGGG 3973 CCCTCTCTCCAGTGCGGCCGGCCGCACTGGAGAGAGGG 3974 CCTCTCTCCAGTGCGGCCC GGGCCGCACTGGAGAGAGG 3975CTCTCTCCAGTGCGGCCCC GGGGCCGCACTGGAGAGAG 3976 TCTCTCCAGTGCGGCCCCGCGGGGCCGCACTGGAGAGA 3977 CTCTCCAGTGCGGCCCCGG CCGGGGCCGCACTGGAGAG 3978TCTCCAGTGCGGCCCCGGC GCCGGGGCCGCACTGGAGA 3979 CTCCAGTGCGGCCCCGGCTAGCCGGGGCCGCACTGGAG 3980 TCCAGTGCGGCCCCGGCTG CAGCCGGGGCCGCACTGGA 3981CCAGTGCGGCCCCGGCTGC GCAGCCGGGGCCGCACTGG 3982 CAGTGCGGCCCCGGCTGCCGGCAGCCGGGGCCGCACTG 3983 AGTGCGGCCCCGGCTGCCT AGGCAGCCGGGGCCGCACT 3984GTGCGGCCCCGGCTGCCTC GAGGCAGCCGGGGCCGCAC 3985 TGCGGCCCCGGCTGCCTCCGGAGGCAGCCGGGGCCGCA 3986 GCGGCCCCGGCTGCCTCCC GGGAGGCAGCCGGGGCCGC 3987CGGCCCCGGCTGCCTCCCC GGGGAGGCAGCCGGGGCCG 3988 GGCCCCGGCTGCCTCCCCCGGGGGAGGCAGCCGGGGCC 3989 GCCCCGGCTGCCTCCCCCA TGGGGGAGGCAGCCGGGGC 3990CCCCGGCTGCCTCCCCCAG CTGGGGGAGGCAGCCGGGG 3991 CCCGGCTGCCTCCCCCAGGCCTGGGGGAGGCAGCCGGG 3992 CCGGCTGCCTCCCCCAGGG CCCTGGGGGAGGCAGCCGG 3993CGGCTGCCTCCCCCAGGGG CCCCTGGGGGAGGCAGCCG 3994 GGCTGCCTCCCCCAGGGGCGCCCCTGGGGGAGGCAGCC 3995 GCTGCCTCCCCCAGGGGCT AGCCCCTGGGGGAGGCAGC 3996CTGCCTCCCCCAGGGGCTT AAGCCCCTGGGGGAGGCAG 3997 TGCCTCCCCCAGGGGCTTTAAAGCCCCTGGGGGAGGCA 3998 GCCTCCCCCAGGGGCTTTG CAAAGCCCCTGGGGGAGGC 3999CCTCCCCCAGGGGCTTTGC GCAAAGCCCCTGGGGGAGG 4000 CTCCCCCAGGGGCTTTGCTAGCAAAGCCCCTGGGGGAG 4001 TCCCCCAGGGGCTTTGCTG CAGCAAAGCCCCTGGGGGA 4002CCCCCAGGGGCTTTGCTGT ACAGCAAAGCCCCTGGGGG 4003 CCCCAGGGGCTTTGCTGTGCACAGCAAAGCCCCTGGGG 4004 CCCAGGGGCTTTGCTGTGG CCACAGCAAAGCCCCTGGG 4005CCAGGGGCTTTGCTGTGGC GCCACAGCAAAGCCCCTGG 4006 CAGGGGCTTTGCTGTGGCTAGCCACAGCAAAGCCCCTG 4007 AGGGGCTTTGCTGTGGCTG CAGCCACAGCAAAGCCCCT 4008GGGGCTTTGCTGTGGCTGC GCAGCCACAGCAAAGCCCC 4009 GGGCTTTGCTGTGGCTGCATGCAGCCACAGCAAAGCCC 4010 GGCTTTGCTGTGGCTGCAG CTGCAGCCACAGCAAAGCC 4011GCTTTGCTGTGGCTGCAGG CCTGCAGCCACAGCAAAGC 4012 CTTTGCTGTGGCTGCAGGATCCTGCAGCCACAGCAAAG 4013 TTTGCTGTGGCTGCAGGAG CTCCTGCAGCCACAGCAAA 4014TTGCTGTGGCTGCAGGAGC GCTCCTGCAGCCACAGCAA 4015 TGCTGTGGCTGCAGGAGCCGGCTCCTGCAGCCACAGCA 4016 GCTGTGGCTGCAGGAGCCC GGGCTCCTGCAGCCACAGC 4017CTGTGGCTGCAGGAGCCCC GGGGCTCCTGCAGCCACAG 4018 TGTGGCTGCAGGAGCCCCATGGGGCTCCTGCAGCCACA 4019 GTGGCTGCAGGAGCCCCAG CTGGGGCTCCTGCAGCCAC 4020TGGCTGCAGGAGCCCCAGC GCTGGGGCTCCTGCAGCCA 4021 GGCTGCAGGAGCCCCAGCCGGCTGGGGCTCCTGCAGCC 4022 GCTGCAGGAGCCCCAGCCT AGGCTGGGGCTCCTGCAGC 4023CTGCAGGAGCCCCAGCCTT AAGGCTGGGGCTCCTGCAG 4024 TGCAGGAGCCCCAGCCTTGCAAGGCTGGGGCTCCTGCA 4025 GCAGGAGCCCCAGCCTTGC GCAAGGCTGGGGCTCCTGC 4026CAGGAGCCCCAGCCTTGCC GGCAAGGCTGGGGCTCCTG 4027 AGGAGCCCCAGCCTTGCCCGGGCAAGGCTGGGGCTCCT 4028 GGAGCCCCAGCCTTGCCCT AGGGCAAGGCTGGGGCTCC 4029GAGCCCCAGCCTTGCCCTC GAGGGCAAGGCTGGGGCTC 4030 AGCCCCAGCCTTGCCCTCGCGAGGGCAAGGCTGGGGCT 4031 GCCCCAGCCTTGCCCTCGG CCGAGGGCAAGGCTGGGGC 4032CCCCAGCCTTGCCCTCGGC GCCGAGGGCAAGGCTGGGG 4033 CCCAGCCTTGCCCTCGGCGCGCCGAGGGCAAGGCTGGG 4034 CCAGCCTTGCCCTCGGCGT ACGCCGAGGGCAAGGCTGG 4035CAGCCTTGCCCTCGGCGTG CACGCCGAGGGCAAGGCTG 4036 AGCCTTGCCCTCGGCGTGGCCACGCCGAGGGCAAGGCT 4037 GCCTTGCCCTCGGCGTGGC GCCACGCCGAGGGCAAGGC 4038CCTTGCCCTCGGCGTGGCT AGCCACGCCGAGGGCAAGG 4039 CTTGCCCTCGGCGTGGCTTAAGCCACGCCGAGGGCAAG 4040 TTGCCCTCGGCGTGGCTTC GAAGCCACGCCGAGGGCAA 4041TGCCCTCGGCGTGGCTTCC GGAAGCCACGCCGAGGGCA 4042 GCCCTCGGCGTGGCTTCCATGGAAGCCACGCCGAGGGC 4043 CCCTCGGCGTGGCTTCCAC GTGGAAGCCACGCCGAGGG 4044CCTCGGCGTGGCTTCCACC GGTGGAAGCCACGCCGAGG 4045 CTCGGCGTGGCTTCCACCTAGGTGGAAGCCACGCCGAG 4046 TCGGCGTGGCTTCCACCTC GAGGTGGAAGCCACGCCGA 4047CGGCGTGGCTTCCACCTCT AGAGGTGGAAGCCACGCCG 4048 GGCGTGGCTTCCACCTCTTAAGAGGTGGAAGCCACGCC 4049 GCGTGGCTTCCACCTCTTC GAAGAGGTGGAAGCCACGC 4050CGTGGCTTCCACCTCTTCC GGAAGAGGTGGAAGCCACG 4051 GTGGCTTCCACCTCTTCCATGGAAGAGGTGGAAGCCAC 4052 TGGCTTCCACCTCTTCCAG CTGGAAGAGGTGGAAGCCA 4053GGCTTCCACCTCTTCCAGG CCTGGAAGAGGTGGAAGCC 4054 GCTTCCACCTCTTCCAGGATCCTGGAAGAGGTGGAAGC 4055 CTTCCACCTCTTCCAGGAG CTCCTGGAAGAGGTGGAAG 4056TTCCACCTCTTCCAGGAGC GCTCCTGGAAGAGGTGGAA 4057 TCCACCTCTTCCAGGAGCATGCTCCTGGAAGAGGTGGA 4058 CCACCTCTTCCAGGAGCAC GTGCTCCTGGAAGAGGTGG 4059CACCTCTTCCAGGAGCACT AGTGCTCCTGGAAGAGGTG 4060 ACCTCTTCCAGGAGCACTGCAGTGCTCCTGGAAGAGGT 4061 CCTCTTCCAGGAGCACTGG CCAGTGCTCCTGGAAGAGG 4062CTCTTCCAGGAGCACTGGA TCCAGTGCTCCTGGAAGAG 4063 TCTTCCAGGAGCACTGGAGCTCCAGTGCTCCTGGAAGA 4064 CTTCCAGGAGCACTGGAGG CCTCCAGTGCTCCTGGAAG 4065TTCCAGGAGCACTGGAGGC GCCTCCAGTGCTCCTGGAA 4066 TCCAGGAGCACTGGAGGCATGCCTCCAGTGCTCCTGGA 4067 CCAGGAGCACTGGAGGCAG CTGCCTCCAGTGCTCCTGG 4068CAGGAGCACTGGAGGCAGG CCTGCCTCCAGTGCTCCTG 4069 AGGAGCACTGGAGGCAGGGCCCTGCCTCCAGTGCTCCT 4070 GGAGCACTGGAGGCAGGGC GCCCTGCCTCCAGTGCTCC 4071GAGCACTGGAGGCAGGGCC GGCCCTGCCTCCAGTGCTC 4072 AGCACTGGAGGCAGGGCCATGGCCCTGCCTCCAGTGCT 4073 GCACTGGAGGCAGGGCCAG CTGGCCCTGCCTCCAGTGC 4074CACTGGAGGCAGGGCCAGC GCTGGCCCTGCCTCCAGTG 4075 ACTGGAGGCAGGGCCAGCCGGCTGGCCCTGCCTCCAGT 4076 CTGGAGGCAGGGCCAGCCT AGGCTGGCCCTGCCTCCAG 4077TGGAGGCAGGGCCAGCCTG CAGGCTGGCCCTGCCTCCA 4078 GGAGGCAGGGCCAGCCTGTACAGGCTGGCCCTGCCTCC 4079 GAGGCAGGGCCAGCCTGTG CACAGGCTGGCCCTGCCTC 4080AGGCAGGGCCAGCCTGTGT ACACAGGCTGGCCCTGCCT 4081 GGCAGGGCCAGCCTGTGTTAACACAGGCTGGCCCTGCC 4082 GCAGGGCCAGCCTGTGTTG CAACACAGGCTGGCCCTGC 4083CAGGGCCAGCCTGTGTTGG CCAACACAGGCTGGCCCTG 4084 AGGGCCAGCCTGTGTTGGTACCAACACAGGCTGGCCCT 4085 GGGCCAGCCTGTGTTGGTG CACCAACACAGGCTGGCCC 4086GGCCAGCCTGTGTTGGTGT ACACCAACACAGGCTGGCC 4087 GCCAGCCTGTGTTGGTGTCGACACCAACACAGGCTGGC 4088 CCAGCCTGTGTTGGTGTCA TGACACCAACACAGGCTGG 4089CAGCCTGTGTTGGTGTCAG CTGACACCAACACAGGCTG 4090 AGCCTGTGTTGGTGTCAGGCCTGACACCAACACAGGCT 4091 GCCTGTGTTGGTGTCAGGG CCCTGACACCAACACAGGC 4092CCTGTGTTGGTGTCAGGGA TCCCTGACACCAACACAGG 4093 CTGTGTTGGTGTCAGGGATATCCCTGACACCAACACAG 4094 TGTGTTGGTGTCAGGGATC GATCCCTGACACCAACACA 4095GTGTTGGTGTCAGGGATCC GGATCCCTGACACCAACAC 4096 TGTTGGTGTCAGGGATCCATGGATCCCTGACACCAACA 4097 GTTGGTGTCAGGGATCCAA TTGGATCCCTGACACCAAC 4098TTGGTGTCAGGGATCCAAA TTTGGATCCCTGACACCAA 4099 TGGTGTCAGGGATCCAAAGCTTTGGATCCCTGACACCA 4100 GGTGTCAGGGATCCAAAGG CCTTTGGATCCCTGACACC 4101GTGTCAGGGATCCAAAGGA TCCTTTGGATCCCTGACAC 4102 TGTCAGGGATCCAAAGGACGTCCTTTGGATCCCTGACA 4103 GTCAGGGATCCAAAGGACA TGTCCTTTGGATCCCTGAC 4104TCAGGGATCCAAAGGACAT ATGTCCTTTGGATCCCTGA 4105 CAGGGATCCAAAGGACATTAATGTCCTTTGGATCCCTG 4106 AGGGATCCAAAGGACATTG CAATGTCCTTTGGATCCCT 4107GGGATCCAAAGGACATTGC GCAATGTCCTTTGGATCCC 4108 GGATCCAAAGGACATTGCATGCAATGTCCTTTGGATCC 4109 GATCCAAAGGACATTGCAG CTGCAATGTCCTTTGGATC 4110ATCCAAAGGACATTGCAGG CCTGCAATGTCCTTTGGAT 4111 TCCAAAGGACATTGCAGGGCCCTGCAATGTCCTTTGGA 4112 CCAAAGGACATTGCAGGGC GCCCTGCAATGTCCTTTGG 4113CAAAGGACATTGCAGGGCA TGCCCTGCAATGTCCTTTG 4114 AAAGGACATTGCAGGGCAATTGCCCTGCAATGTCCTTT 4115 AAGGACATTGCAGGGCAAC GTTGCCCTGCAATGTCCTT 4116AGGACATTGCAGGGCAACC GGTTGCCCTGCAATGTCCT 4117 GGACATTGCAGGGCAACCTAGGTTGCCCTGCAATGTCC 4118 GACATTGCAGGGCAACCTG CAGGTTGCCCTGCAATGTC 4119ACATTGCAGGGCAACCTGT ACAGGTTGCCCTGCAATGT 4120 CATTGCAGGGCAACCTGTGCACAGGTTGCCCTGCAATG 4121 ATTGCAGGGCAACCTGTGG CCACAGGTTGCCCTGCAAT 4122TTGCAGGGCAACCTGTGGG CCCACAGGTTGCCCTGCAA 4123 TGCAGGGCAACCTGTGGGGCCCCACAGGTTGCCCTGCA 4124 GCAGGGCAACCTGTGGGGG CCCCCACAGGTTGCCCTGC 4125CAGGGCAACCTGTGGGGGA TCCCCCACAGGTTGCCCTG 4126 AGGGCAACCTGTGGGGGACGTCCCCCACAGGTTGCCCT 4127 GGGCAACCTGTGGGGGACA TGTCCCCCACAGGTTGCCC 4128GGCAACCTGTGGGGGACAG CTGTCCCCCACAGGTTGCC 4129 GCAACCTGTGGGGGACAGATCTGTCCCCCACAGGTTGC 4130 CAACCTGTGGGGGACAGAA TTCTGTCCCCCACAGGTTG 4131AACCTGTGGGGGACAGAAG CTTCTGTCCCCCACAGGTT 4132 ACCTGTGGGGGACAGAAGCGCTTCTGTCCCCCACAGGT 4133 CCTGTGGGGGACAGAAGCT AGCTTCTGTCCCCCACAGG 4134CTGTGGGGGACAGAAGCTC GAGCTTCTGTCCCCCACAG 4135 TGTGGGGGACAGAAGCTCTAGAGCTTCTGTCCCCCACA 4136 GTGGGGGACAGAAGCTCTT AAGAGCTTCTGTCCCCCAC 4137TGGGGGACAGAAGCTCTTG CAAGAGCTTCTGTCCCCCA 4138 GGGGGACAGAAGCTCTTGGCCAAGAGCTTCTGTCCCCC 4139 GGGGACAGAAGCTCTTGGG CCCAAGAGCTTCTGTCCCC 4140GGGACAGAAGCTCTTGGGG CCCCAAGAGCTTCTGTCCC 4141 GGACAGAAGCTCTTGGGGCGCCCCAAGAGCTTCTGTCC 4142 GACAGAAGCTCTTGGGGCA TGCCCCAAGAGCTTCTGTC 4143ACAGAAGCTCTTGGGGCAC GTGCCCCAAGAGCTTCTGT 4144 CAGAAGCTCTTGGGGCACTAGTGCCCCAAGAGCTTCTG 4145 AGAAGCTGTTGGGGCACTT AAGTGCCCCAAGAGCTTCT 4146GAAGCTCTTGGGGCACTTG CAAGTGCCCCAAGAGCTTC 4147 AAGCTCTTGGGGCACTTGGCCAAGTGCCCCAAGAGCTT 4148 AGCTCTTGGGGCACTTGGA TCCAAGTGCCCCAAGAGCT 4149GCTCTTGGGGCACTTGGAG CTCCAAGTGCCCCAAGAGC 4150 CTCTTGGGGCACTTGGAGGCCTCCAAGTGCCCCAAGAG 4151 TCTTGGGGCACTTGGAGGC GCCTCCAAGTGCCCCAAGA 4152CTTGGGGCACTTGGAGGCC GGCCTCCAAGTGCCCCAAG 4153 TTGGGGCACTTGGAGGCCATGGCCTCCAAGTGCCCCAA 4154 TGGGGCACTTGGAGGCCAG CTGGCCTCCAAGTGCCCCA 4155GGGGCACTTGGAGGCCAGG CCTGGCCTCCAAGTGCCCC 4156 GGGCACTTGGAGGCCAGGTACCTGGCCTCCAAGTGCCC 4157 GGCACTTGGAGGCCAGGTG CACCTGGCCTCCAAGTGCC 4158GCACTTGGAGGCCAGGTGC GCACCTGGCCTCCAAGTGC 4159 CACTTGGAGGCCAGGTGCATGCACCTGGCCTCCAAGTG 4160 ACTTGGAGGCCAGGTGCAG CTGCACCTGGCCTCCAAGT 4161CTTGGAGGCCAGGTGCAGG CCTGCACCTGGCCTCCAAG 4162 TTGGAGGCCAGGTGCAGGCGCCTGCACCTGGCCTCCAA 4163 TGGAGGCCAGGTGCAGGCG CGCCTGCACCTGGCCTCCA 4164GGAGGCCAGGTGCAGGCGC GCGCCTGCACCTGGCCTCC 4165 GAGGCCAGGTGCAGGCGCTAGCGCCTGCACCTGGCCTC 4166 AGGCCAGGTGCAGGCGCTG CAGCGCCTGCACCTGGCCT 4167GGCCAGGTGCAGGCGCTGA TCAGCGCCTGCACCTGGCC 4168 GCCAGGTGCAGGCGCTGAGCTCAGCGCCTGCACCTGGC 4169 CCAGGTGCAGGCGCTGAGC GCTCAGCGCCTGCACCTGG 4170CAGGTGCAGGCGCTGAGCC GGCTCAGCGCCTGCACCTG 4171 AGGTGCAGGCGCTGAGCCCGGGCTCAGCGCCTGCACCT 4172 GGTGCAGGCGCTGAGCCCC GGGGCTCAGCGCCTGCACC 4173GTGCAGGCGCTGAGCCCCC GGGGGCTCAGCGCCTGCAC 4174 TGCAGGCGCTGAGCCCCCTAGGGGGCTCAGCGCCTGCA 4175 GCAGGCGCTGAGCCCCCTC GAGGGGGCTCAGCGCCTGC 4176CAGGCGCTGAGCCCCCTCG CGAGGGGGCTCAGCGCCTG 4177 AGGCGCTGAGCCCCCTCGGCCGAGGGGGCTCAGCGCCT 4178 GGCGCTGAGCCCCCTCGGA TCCGAGGGGGCTCAGCGCC 4179GCGCTGAGCCCCCTCGGAC GTCCGAGGGGGCTCAGCGC 4180 CGCTGAGCCCCCTCGGACCGGTCCGAGGGGGCTCAGCG 4181 GCTGAGCCCCCTCGGACCT AGGTCCGAGGGGGCTCAGC 4182CTGAGCCCCCTCGGACCTC GAGGTCCGAGGGGGCTCAG 4183 TGAGCCCCCTCGGACCTCCGGAGGTCCGAGGGGGCTCA 4184 GAGCCCCCTCGGACCTCCC GGGAGGTCCGAGGGGGCTC 4185AGCCCCCTCGGACCTCCCC GGGGAGGTCCGAGGGGGCT 4186 GCCCCCTCGGACCTCCCCATGGGGAGGTCCGAGGGGGC 4187 CCCCCTCGGACCTCCCCAG CTGGGGAGGTCCGAGGGGG 4188CCCCTCGGACCTCCCCAGC GCTGGGGAGGTCCGAGGGG 4189 CCCTCGGACCTCCCCAGCCGGCTGGGGAGGTCCGAGGG 4190 CCTCGGACCTCCCCAGCCC GGGCTGGGGAGGTCCGAGG 4191CTCGGACCTCCCCAGCCCA TGGGCTGGGGAGGTCCGAG 4192 TCGGACCTCCCCAGCCCAGCTGGGCTGGGGAGGTCCGA 4193 CGGACCTCCCCAGCCCAGC GCTGGGCTGGGGAGGTCCG 4194GGACCTCCCCAGCCCAGCA TGCTGGGCTGGGGAGGTCC 4195 GACCTCCCCAGCCCAGCAGCTGCTGGGCTGGGGAGGTC 4196 ACCTCCCCAGCCCAGCAGC GCTGCTGGGCTGGGGAGGT 4197CCTCCCCAGCCCAGCAGCC GGCTGCTGGGCTGGGGAGG 4198 CTCCCCAGCCCAGCAGCCTAGGCTGCTGGGCTGGGGAG 4199 TCCCCAGCCCAGCAGCCTG CAGGCTGCTGGGCTGGGGA 4200CCCCAGCCCAGCAGCCTGG CCAGGCTGCTGGGCTGGGG 4201 CCCAGCCCAGCAGCCTGGGCCCAGGCTGCTGGGCTGGG 4202 CCAGCCCAGCAGCCTGGGC GCCCAGGCTGCTGGGCTGG 4203CAGCCCAGCAGCCTGGGCA TGCCCAGGCTGCTGGGCTG 4204 AGCCCAGCAGCCTGGGCAGCTGCCCAGGCTGCTGGGCT 4205 GCCCAGCAGCCTGGGCAGC GCTGCCCAGGCTGCTGGGC 4206CCCAGCAGCCTGGGCAGCA TGCTGCCCAGGCTGCTGGG 4207 CCAGCAGCCTGGGCAGCACGTGCTGCCCAGGCTGCTGG 4208 CAGCAGCCTGGGCAGCACA TGTGCTGCCCAGGCTGCTG 4209AGCAGCCTGGGCAGCACAA TTGTGCTGCCCAGGCTGCT 4210 GCAGCCTGGGCAGCACAACGTTGTGCTGCCCAGGCTGC 4211 CAGCCTGGGCAGCACAACA TGTTGTGCTGCCCAGGCTG 4212AGCCTGGGCAGCACAACAT ATGTTGTGCTGCCCAGGCT 4213 GCCTGGGCAGCACAACATTAATGTTGTGCTGCCCAGGC 4214 CCTGGGCAGCACAACATTC GAATGTTGTGCTGCCCAGG 4215CTGGGCAGCACAACATTCT AGAATGTTGTGCTGCCCAG 4216 TGGGCAGCACAACATTCTGCAGAATGTTGTGCTGCCCA 4217 GGGCAGCACAACATTCTGG CCAGAATGTTGTGCTGCCC 4218GGCAGCACAACATTCTGGG CCCAGAATGTTGTGCTGCC 4219 GCAGCACAACATTCTGGGATCCCAGAATGTTGTGCTGC 4220 CAGCACAACATTCTGGGAG CTCCCAGAATGTTGTGCTG 4221AGCACAACATTCTGGGAGG CCTCCCAGAATGTTGTGCT 4222 GCACAACATTCTGGGAGGGCCCTCCCAGAATGTTGTGC 4223 CACAACATTCTGGGAGGGC GCCCTCCCAGAATGTTGTG 4224ACAACATTCTGGGAGGGCT AGCCCTCCCAGAATGTTGT 4225 CAACATTCTGGGAGGGCTTAAGCCCTCCCAGAATGTTG 4226 AACATTCTGGGAGGGCTTC GAAGCCCTCCCAGAATGTT 4227ACATTCTGGGAGGGCTTCT AGAAGCCCTCCCAGAATGT 4228 CATTCTGGGAGGGCTTCTCGAGAAGCCCTCCCAGAATG 4229 ATTCTGGGAGGGCTTCTCC GGAGAAGCCCTCCCAGAAT 4230TTCTGGGAGGGCTTCTCCT AGGAGAAGCCCTCCCAGAA 4231 TCTGGGAGGGCTTCTCCTGCAGGAGAAGCCCTCCCAGA 4232 CTGGGAGGGCTTCTCCTGG CCAGGAGAAGCCCTCCCAG 4233TGGGAGGGCTTCTCCTGGC GCCAGGAGAAGCCCTCCCA 4234 GGGAGGGCTTCTCCTGGCCGGCCAGGAGAAGCCCTCCC 4235 GGAGGGCTTCTCCTGGCCT AGGCCAGGAGAAGCCCTCC 4236GAGGGCTTCTCCTGGCCTG CAGGCCAGGAGAAGCCCTC 4237 AGGGCTTCTCCTGGCCTGATCAGGCCAGGAGAAGCCCT 4238 GGGCTTCTCCTGGCCTGAG CTCAGGCCAGGAGAAGCCC 4239GGCTTCTCCTGGCCTGAGC GCTCAGGCCAGGAGAAGCC 4240 GCTTCTCCTGGCCTGAGCTAGCTCAGGCCAGGAGAAGC 4241 CTTCTCCTGGCCTGAGCTT AAGCTCAGGCCAGGAGAAG 4242TTCTCCTGGCCTGAGCTTC GAAGCTCAGGCCAGGAGAA 4243 TCTCCTGGCCTGAGCTTCGCGAAGCTCAGGCCAGGAGA 4244 CTCCTGGCCTGAGCTTCGC GCGAAGCTCAGGCCAGGAG 4245TCCTGGCCTGAGCTTCGCC GGCGAAGCTCAGGCCAGGA 4246 CCTGGCCTGAGCTTCGCCCGGGCGAAGCTCAGGCCAGG 4247 CTGGCCTGAGCTTCGCCCA TGGGCGAAGCTCAGGCCAG 4248TGGCCTGAGCTTCGCCCAA TTGGGCGAAGCTCAGGCCA 4249 GGCCTGAGCTTCGCCCAAATTTGGGCGAAGCTCAGGCC 4250 GCCTGAGCTTCGCCCAAAG CTTTGGGCGAAGCTCAGGC 4251CCTGAGCTTCGCCCAAAGT ACTTTGGGCGAAGCTCAGG 4252 CTGAGCTTCGCCCAAAGTCGACTTTGGGCGAAGCTCAG 4253 TGAGCTTCGCCCAAAGTCA TGACTTTGGGCGAAGCTCA 4254GAGCTTCGCCCAAAGTCAG CTGACTTTGGGCGAAGCTC 4255 AGCTTCGCCCAAAGTCAGATCTGACTTTGGGCGAAGCT 4256 GCTTCGCCCAAAGTCAGAC GTCTGACTTTGGGCGAAGC 4257CTTCGCCCAAAGTCAGACG CGTCTGACTTTGGGCGAAG 4258 TTCGCCCAAAGTCAGACGATCGTCTGACTTTGGGCGAA 4259 TCGCCCAAAGTCAGACGAG CTCGTCTGACTTTGGGCGA 4260CGCCCAAAGTCAGACGAGG CCTCGTCTGACTTTGGGCG 4261 GCCCAAAGTCAGACGAGGGCCCTCGTCTGACTTTGGGC 4262 CCCAAAGTCAGACGAGGGC GCCCTCGTCTGACTTTGGG 4263CCAAAGTCAGACGAGGGCT AGCCCTCGTCTGACTTTGG 4264 CAAAGTCAGACGAGGGCTCGAGCCCTCGTCTGACTTTG 4265 AAAGTCAGACGAGGGCTCT AGAGCCCTCGTCTGACTTT 4266AAGTCAGACGAGGGCTCTG CAGAGCCCTCGTCTGACTT 4267 AGTCAGACGAGGGCTCTGTACAGAGCCCTCGTCTGACT 4268 GTCAGACGAGGGCTCTGTC GACAGAGCCCTCGTCTGAC 4269TCAGACGAGGGCTCTGTCC GGACAGAGCCCTCGTCTGA 4270 CAGACGAGGGCTCTGTCCTAGGACAGAGCCCTCGTCTG 4271 AGACGAGGGCTCTGTCCTC GAGGACAGAGCCCTCGTCT 4272GACGAGGGCTCTGTCCTCC GGAGGACAGAGCCCTCGTC 4273 ACGAGGGCTCTGTCCTCCTAGGAGGACAGAGCCCTCGT 4274 CGAGGGCTCTGTCCTCCTG CAGGAGGACAGAGCCCTCG 4275GAGGGCTCTGTCCTCCTGC GCAGGAGGACAGAGCCCTC 4276 AGGGCTCTGTCCTCCTGCTAGCAGGAGGACAGAGCCCT 4277 GGGCTCTGTCCTCCTGCTG CAGCAGGAGGACAGAGCCC 4278GGCTCTGTCCTCCTGCTGC GCAGCAGGAGGACAGAGCC 4279 GCTCTGTCCTCCTGCTGCATGCAGCAGGAGGACAGAGC 4280 CTCTGTCCTCCTGCTGCAC GTGCAGCAGGAGGACAGAG 4281TCTGTCCTCCTGCTGCACC GGTGCAGCAGGAGGACAGA 4282 CTGTCCTCCTGCTGCACCGCGGTGCAGCAGGAGGACAG 4283 TGTCCTCCTGCTGCACCGA TCGGTGCAGCAGGAGGACA 4284GTCCTCCTGCTGCACCGAG CTCGGTGCAGCAGGAGGAC 4285 TCCTCCTGCTGCACCGAGCGCTCGGTGCAGCAGGAGGA 4286 CCTCCTGCTGCACCGAGCT AGCTCGGTGCAGCAGGAGG 4287CTCCTGCTGCACCGAGCTT AAGCTCGGTGCAGCAGGAG 4288 TCCTGCTGCACCGAGCTTTAAAGCTCGGTGCAGCAGGA 4289 CCTGCTGCACCGAGCTTTG CAAAGCTCGGTGCAGCAGG 4290CTGCTGCACCGAGCTTTGG CCAAAGCTCGGTGCAGCAG 4291 TGCTGCACCGAGCTTTGGGCCCAAAGCTCGGTGCAGCA 4292 GCTGCACCGAGCTTTGGGG CCCCAAAGCTCGGTGCAGC 4293CTGCACCGAGCTTTGGGGG CCCCCAAAGCTCGGTGCAG 4294 TGCACCGAGCTTTGGGGGATCCCCCAAAGCTCGGTGCA 4295 GCACCGAGCTTTGGGGGAT ATCCCCCAAAGCTCGGTGC 4296CACCGAGCTTTGGGGGATG CATCCCCCAAAGCTCGGTG 4297 ACCGAGCTTTGGGGGATGATCATCCCCCAAAGCTCGGT 4298 CCGAGCTTTGGGGGATGAG CTCATCCCCCAAAGCTCGG 4299CGAGCTTTGGGGGATGAGG CCTCATCCCCCAAAGCTCG 4300 GAGCTTTGGGGGATGAGGATCCTCATCCCCCAAAGCTC 4301 AGCTTTGGGGGATGAGGAC GTCCTCATCCCCCAAAGCT 4302GCTTTGGGGGATGAGGACA TGTCCTCATCCCCCAAAGC 4303 CTTTGGGGGATGAGGACACGTGTCCTCATCCCCCAAAG 4304 TTTGGGGGATGAGGACACC GGTGTCCTCATCCCCCAAA 4305TTGGGGGATGAGGACACCA TGGTGTCCTCATCCCCCAA 4306 TGGGGGATGAGGACACCAGCTGGTGTCCTCATCCCCCA 4307 GGGGGATGAGGACACCAGC GCTGGTGTCCTCATCCCCC 4308GGGGATGAGGACACCAGCA TGCTGGTGTCCTCATCCCC 4309 GGGATGAGGACACCAGCAGCTGCTGGTGTCCTCATCCC 4310 GGATGAGGACACCAGCAGG CCTGCTGGTGTCCTCATCC 4311GATGAGGACACCAGCAGGG CCCTGCTGGTGTCCTCATC 4312 ATGAGGACACCAGCAGGGTACCCTGCTGGTGTCCTCAT 4313 TGAGGACACCAGCAGGGTG CACCCTGCTGGTGTCCTCA 4314GAGGACACCAGCAGGGTGG CCACCCTGCTGGTGTCCTC 4315 AGGACACCAGCAGGGTGGATCCACCCTGCTGGTGTCCT 4316 GGACACCAGCAGGGTGGAG CTCCACCCTGCTGGTGTCC 4317GACACCAGCAGGGTGGAGA TCTCCACCCTGCTGGTGTC 4318 ACACCAGCAGGGTGGAGAATTCTCCACCCTGCTGGTGT 4319 CACCAGCAGGGTGGAGAAC GTTCTCCACCCTGCTGGTG 4320ACCAGCAGGGTGGAGAACC GGTTCTCCACCCTGCTGGT 4321 CCAGCAGGGTGGAGAACCTAGGTTCTCCACCCTGCTGG 4322 CAGCAGGGTGGAGAACCTA TAGGTTCTCCACCCTGCTG 4323AGCAGGGTGGAGAACCTAG CTAGGTTCTCCACCCTGCT 4324 GCAGGGTGGAGAACCTAGCGCTAGGTTCTCCACCCTGC 4325 CAGGGTGGAGAACCTAGCT AGCTAGGTTCTCCACCCTG 4326AGGGTGGAGAACCTAGCTG CAGCTAGGTTCTCCACCCT 4327 GGGTGGAGAACCTAGCTGCGCAGCTAGGTTCTCCACCC 4328 GGTGGAGAACCTAGCTGCC GGCAGCTAGGTTCTCCACC 4329GTGGAGAACCTAGCTGCCA TGGCAGCTAGGTTCTCCAC 4330 TGGAGAACCTAGCTGCCAGCTGGCAGCTAGGTTCTCCA 4331 GGAGAACCTAGCTGCCAGT ACTGGCAGCTAGGTTCTCC 4332GAGAACCTAGCTGCCAGTC GACTGGCAGCTAGGTTCTC 4333 AGAACCTAGCTGCCAGTCTAGACTGGCAGCTAGGTTCT 4334 GAACCTAGCTGCCAGTCTG CAGACTGGCAGCTAGGTTC 4335AACCTAGCTGCCAGTCTGC GCAGACTGGCAGCTAGGTT 4336 ACCTAGCTGCCAGTCTGCCGGCAGACTGGCAGCTAGGT 4337 CCTAGCTGCCAGTCTGCCA TGGCAGACTGGCAGCTAGG 4338CTAGCTGCCAGTCTGCCAC GTGGCAGACTGGCAGCTAG 4339 TAGCTGCCAGTCTGCCACTAGTGGCAGACTGGCAGCTA 4340 AGCTGCCAGTCTGCCACTT AAGTGGCAGACTGGCAGCT 4341GCTGCCAGTCTGCCACTTC GAAGTGGCAGACTGGCAGC 4342 CTGCCAGTCTGCCACTTCCGGAAGTGGCAGACTGGCAG 4343 TGCCAGTCTGCCACTTCCG CGGAAGTGGCAGACTGGCA 4344GCCAGTCTGCCACTTCCGG CCGGAAGTGGCAGACTGGC 4345 CCAGTCTGCCACTTCCGGATCCGGAAGTGGCAGACTGG 4346 CAGTCTGCCACTTCCGGAG CTCCGGAAGTGGCAGACTG 4347AGTCTGCCACTTCCGGAGT ACTCCGGAAGTGGCAGACT 4348 GTCTGCCACTTCCGGAGTATACTCCGGAAGTGGCAGAC 4349 TCTGCCACTTCCGGAGTAC GTACTCCGGAAGTGGCAGA 4350CTGCCACTTCCGGAGTACT AGTACTCCGGAAGTGGCAG 4351 TGCCACTTCCGGAGTACTGCAGTACTCCGGAAGTGGCA 4352 GCCACTTCCGGAGTACTGC GCAGTACTCCGGAAGTGGC 4353CCACTTCCGGAGTACTGCG CGCAGTACTCCGGAAGTGG 4354 CACTTCCGGAGTACTGCGCGCGCAGTACTCCGGAAGTG 4355 ACTTCCGGAGTACTGCGCC GGCGCAGTACTCCGGAAGT 4356CTTCCGGAGTACTGCGCCC GGGCGCAGTACTCCGGAAG 4357 TTCCGGAGTACTGCGCCCTAGGGCGCAGTACTCCGGAA 4358 TCCGGAGTACTGCGCCCTC GAGGGCGCAGTACTCCGGA 4359CCGGAGTACTGCGCCCTCC GGAGGGCGCAGTACTCCGG 4360 CGGAGTACTGCGCCCTCCATGGAGGGCGCAGTACTCCG 4361 GGAGTACTGCGCCCTCCAT ATGGAGGGCGCAGTACTCC 4362GAGTACTGCGCCCTCCATG CATGGAGGGCGCAGTACTC 4363 AGTACTGCGCCCTCCATGGCCATGGAGGGCGCAGTACT 4364 GTACTGCGCCCTCCATGGA TCCATGGAGGGCGCAGTAC 4365TACTGCGCCCTCCATGGAA TTCCATGGAGGGCGCAGTA 4366 ACTGCGCCCTCCATGGAAATTTCCATGGAGGGCGCAGT 4367 CTGCGCCCTCCATGGAAAA TTTTCCATGGAGGGCGCAG 4368TGCGCCCTCCATGGAAAAC GTTTTCCATGGAGGGCGCA 4369 GCGCCCTCCATGGAAAACTAGTTTTCCATGGAGGGCGC 4370 CGCCCTCCATGGAAAACTC GAGTTTTCCATGGAGGGCG 4371GCCCTCCATGGAAAACTCA TGAGTTTTCCATGGAGGGC 4372 CCCTCCATGGAAAACTCAATTGAGTTTTCCATGGAGGG 4373 CCTCCATGGAAAACTCAAC GTTGAGTTTTCCATGGAGG 4374CTCCATGGAAAACTCAACC GGTTGAGTTTTCCATGGAG 4375 TCCATGGAAAACTCAACCTAGGTTGAGTTTTCCATGGA 4376 CCATGGAAAACTCAACCTG CAGGTTGAGTTTTCCATGG 4377CATGGAAAACTCAACCTGG CCAGGTTGAGTTTTCCATG 4378 ATGGAAAACTCAACCTGGCGCCAGGTTGAGTTTTCCAT 4379 TGGAAAACTCAACCTGGCT AGCCAGGTTGAGTTTTCCA 4380GGAAAACTCAACCTGGCTT AAGCCAGGTTGAGTTTTCC 4381 GAAAACTCAACCTGGCTTCGAAGCCAGGTTGAGTTTTC 4382 AAAACTCAACCTGGCTTCC GGAAGCCAGGTTGAGTTTT 4383AAACTCAACCTGGCTTCCT AGGAAGCCAGGTTGAGTTT 4384 AACTCAACCTGGCTTCCTATAGGAAGCCAGGTTGAGTT 4385 ACTCAACCTGGCTTCCTAC GTAGGAAGCCAGGTTGAGT 4386CTCAACCTGGCTTCCTACC GGTAGGAAGCCAGGTTGAG 4387 TCAACCTGGCTTCCTACCTAGGTAGGAAGCCAGGTTGA 4388 CAACCTGGCTTCCTACCTC GAGGTAGGAAGCCAGGTTG 4389AACCTGGCTTCCTACCTCC GGAGGTAGGAAGCCAGGTT 4390 ACCTGGCTTCCTACCTCCCGGGAGGTAGGAAGCCAGGT 4391 CCTGGCTTCCTACCTCCCA TGGGAGGTAGGAAGCCAGG 4392CTGGCTTCCTACCTCCCAC GTGGGAGGTAGGAAGCCAG 4393 TGGCTTCCTACCTCCCACCGGTGGGAGGTAGGAAGCCA 4394 GGCTTCCTACCTCCCACCG CGGTGGGAGGTAGGAAGCC 4395GCTTCCTACCTCCCACCGG CCGGTGGGAGGTAGGAAGC 4396 CTTCCTACCTCCCACCGGGCCCGGTGGGAGGTAGGAAG 4397 TTCCTACCTCCCACCGGGC GCCCGGTGGGAGGTAGGAA 4398TCCTACCTCCCACCGGGCC GGCCCGGTGGGAGGTAGGA 4399 CCTACCTCCCACCGGGCCTAGGCCCGGTGGGAGGTAGG 4400 CTACCTCCCACCGGGCCTT AAGGCCCGGTGGGAGGTAG 4401TACCTCCCACCGGGCCTTG CAAGGCCCGGTGGGAGGTA 4402 ACCTCCCACCGGGCCTTGCGCAAGGCCCGGTGGGAGGT 4403 CCTCCCACCGGGCCTTGCC GGCAAGGCCCGGTGGGAGG 4404CTCCCACCGGGCCTTGCCC GGGCAAGGCCCGGTGGGAG 4405 TCCCACCGGGCCTTGCCCTAGGGCAAGGCCCGGTGGGA 4406 CCCACCGGGCCTTGCCCTG CAGGGCAAGGCCCGGTGGG 4407CCACCGGGCCTTGCCCTGC GCAGGGCAAGGCCCGGTGG 4408 CACCGGGCCTTGCCCTGCGCGCAGGGCAAGGCCCGGTG 4409 ACCGGGCCTTGCCCTGCGT ACGCAGGGCAAGGCCCGGT 4410CCGGGCCTTGCCCTGCGTC GACGCAGGGCAAGGCCCGG 4411 CGGGCCTTGCCCTGCGTCCGGACGCAGGGCAAGGCCCG 4412 GGGCCTTGCCCTGCGTCCA TGGACGCAGGGCAAGGCCC 4413GGCCTTGCCCTGCGTCCAC GTGGACGCAGGGCAAGGCC 4414 GCCTTGCCCTGCGTCCACTAGTGGACGCAGGGCAAGGC 4415 CCTTGCCCTGCGTCCACTG CAGTGGACGCAGGGCAAGG 4416CTTGCCCTGCGTCCACTGG CCAGTGGACGCAGGGCAAG 4417 TTGCCCTGCGTCCACTGGATCCAGTGGACGCAGGGCAA 4418 TGCCCTGCGTCCACTGGAG CTCCAGTGGACGCAGGGCA 4419GCCCTGCGTCCACTGGAGC GCTCCAGTGGACGCAGGGC 4420 CCCTGCGTCCACTGGAGCCGGCTCCAGTGGACGCAGGG 4421 CCTGCGTCCACTGGAGCCC GGGCTCCAGTGGACGCAGG 4422CTGCGTCCACTGGAGCCCC GGGGCTCCAGTGGACGCAG 4423 TGCGTCCACTGGAGCCCCATGGGGCTCCAGTGGACGCA 4424 GCGTCCACTGGAGCCCCAG CTGGGGCTCCAGTGGACGC 4425CGTCCACTGGAGCCCCAGC GCTGGGGCTCCAGTGGACG 4426 GTCCACTGGAGCCCCAGCTAGCTGGGGCTCCAGTGGAC 4427 TCCACTGGAGCCCCAGCTC GAGCTGGGGCTCCAGTGGA 4428CCACTGGAGCCCCAGCTCT AGAGCTGGGGCTCCAGTGG 4429 CACTGGAGCCCCAGCTCTGCAGAGCTGGGGCTCCAGTG 4430 ACTGGAGCCCCAGCTCTGG CCAGAGCTGGGGCTCCAGT 4431CTGGAGCCCCAGCTCTGGG CCCAGAGCTGGGGCTCCAG 4432 TGGAGCCCCAGCTCTGGGCGCCCAGAGCTGGGGCTCCA 4433 GGAGCCCCAGCTCTGGGCA TGCCCAGAGCTGGGGCTCC 4434GAGCCCCAGCTCTGGGCAG CTGCCCAGAGCTGGGGCTC 4435 AGCCCCAGCTCTGGGCAGCGCTGCCCAGAGCTGGGGCT 4436 GCCCCAGCTCTGGGCAGCC GGCTGCCCAGAGCTGGGGC 4437CCCCAGCTCTGGGCAGCCT AGGCTGCCCAGAGCTGGGG 4438 CCCAGCTCTGGGCAGCCTATAGGCTGCCCAGAGCTGGG 4439 CCAGCTCTGGGCAGCCTAT ATAGGCTGCCCAGAGCTGG 4440CAGCTCTGGGCAGCCTATG CATAGGCTGCCCAGAGCTG 4441 AGCTCTGGGCAGCCTATGGCCATAGGCTGCCCAGAGCT 4442 GCTCTGGGCAGCCTATGGT ACCATAGGCTGCCCAGAGC 4443CTCTGGGCAGCCTATGGTG CACCATAGGCTGCCCAGAG 4444 TCTGGGCAGCCTATGGTGTACACCATAGGCTGCCCAGA 4445 CTGGGCAGCCTATGGTGTG CACACCATAGGCTGCCCAG 4446TGGGCAGCCTATGGTGTGA TCACACCATAGGCTGCCCA 4447 GGGCAGCCTATGGTGTGAGCTCACACCATAGGCTGCCC 4448 GGCAGCCTATGGTGTGAGC GCTCACACCATAGGCTGCC 4449GCAGCCTATGGTGTGAGCC GGCTCACACCATAGGCTGC 4450 CAGCCTATGGTGTGAGCCCGGGCTCACACCATAGGCTG 4451 AGCCTATGGTGTGAGCCCG CGGGCTCACACCATAGGCT 4452GCCTATGGTGTGAGCCCGC GCGGGCTCACACCATAGGC 4453 CCTATGGTGTGAGCCCGCATGCGGGCTCACACCATAGG 4454 CTATGGTGTGAGCCCGCAC GTGCGGGCTCACACCATAG 4455TATGGTGTGAGCCCGCACC GGTGCGGGCTCACACCATA 4456 ATGGTGTGAGCCCGCACCGCGGTGCGGGCTCACACCAT 4457 TGGTGTGAGCCCGCACCGG CCGGTGCGGGCTCACACCA 4458GGTGTGAGCCCGCACCGGG CCCGGTGCGGGCTCACACC 4459 GTGTGAGCCCGCACCGGGGCCCCGGTGCGGGCTCACAC 4460 TGTGAGCCCGCACCGGGGA TCCCCGGTGCGGGCTCACA 4461GTGAGCCCGCACCGGGGAC GTCCCCGGTGCGGGCTCAC 4462 TGAGCCCGCACCGGGGACATGTCCCCGGTGCGGGCTCA 4463 GAGCCCGCACCGGGGACAC GTGTCCCCGGTGCGGGCTC 4464AGCCCGCACCGGGGACACC GGTGTCCCCGGTGCGGGCT 4465 GCCCGCACCGGGGACACCTAGGTGTCCCCGGTGCGGGC 4466 CCCGCACCGGGGACACCTG CAGGTGTCCCCGGTGCGGG 4467CCGCACCGGGGACACCTGG CCAGGTGTCCCCGGTGCGG 4468 CGCACCGGGGACACCTGGGCCCAGGTGTCCCCGGTGCG 4469 GCACCGGGGACACCTGGGG CCCCAGGTGTCCCCGGTGC 4470CACCGGGGACACCTGGGGA TCCCCAGGTGTCCCCGGTG 4471 ACCGGGGACACCTGGGGACGTCCCCAGGTGTCCCCGGT 4472 CCGGGGACACCTGGGGACC GGTCCCCAGGTGTCCCCGG 4473CGGGGACACCTGGGGACCA TGGTCCCCAGGTGTCCCCG 4474 GGGGACACCTGGGGACCAATTGGTCCCCAGGTGTCCCC 4475 GGGACACCTGGGGACCAAG CTTGGTCCCCAGGTGTCCC 4476GGACACCTGGGGACCAAGA TCTTGGTCCCCAGGTGTCC 4477 GACACCTGGGGACCAAGAATTCTTGGTCCCCAGGTGTC 4478 ACACCTGGGGACCAAGAAC GTTCTTGGTCCCCAGGTGT 4479CACCTGGGGACCAAGAACC GGTTCTTGGTCCCCAGGTG 4480 ACCTGGGGACCAAGAACCTAGGTTCTTGGTCCCCAGGT 4481 CCTGGGGACCAAGAACCTC GAGGTTCTTGGTCCCCAGG 4482CTGGGGACCAAGAACCTCT AGAGGTTCTTGGTCCCCAG 4483 TGGGGACCAAGAACCTCTGCAGAGGTTCTTGGTCCCCA 4484 GGGGACCAAGAACCTCTGT ACAGAGGTTCTTGGTCCCC 4485GGGACCAAGAACCTCTGTG CACAGAGGTTCTTGGTCCC 4486 GGACCAAGAACCTCTGTGTACACAGAGGTTCTTGGTCC 4487 GACCAAGAACCTCTGTGTG CACACAGAGGTTCTTGGTC 4488ACCAAGAACCTCTGTGTGG CCACACAGAGGTTCTTGGT 4489 CCAAGAACCTCTGTGTGGATCCACACAGAGGTTCTTGG 4490 CAAGAACCTCTGTGTGGAG CTCCACACAGAGGTTCTTG 4491AAGAACCTCTGTGTGGAGG CCTCCACACAGAGGTTCTT 4492 AGAACCTCTGTGTGGAGGTACCTCCACACAGAGGTTCT 4493 GAACCTCTGTGTGGAGGTG CACCTCCACACAGAGGTTC 4494AACCTCTGTGTGGAGGTGG CCACCTCCACACAGAGGTT 4495 ACCTCTGTGTGGAGGTGGCGCCACCTCCACACAGAGGT 4496 CCTCTGTGTGGAGGTGGCC GGCCACCTCCACACAGAGG 4497CTCTGTGTGGAGGTGGCCG CGGCCACCTCCACACAGAG 4498 TCTGTGTGGAGGTGGCCGATCGGCCACCTCCACACAGA 4499 CTGTGTGGAGGTGGCCGAC GTCGGCCACCTCCACACAG 4500TGTGTGGAGGTGGCCGACC GGTCGGCCACCTCCACACA 4501 GTGTGGAGGTGGCCGACCTAGGTCGGCCACCTCCACAC 4502 TGTGGAGGTGGCCGACCTG CAGGTCGGCCACCTCCACA 4503GTGGAGGTGGCCGACCTGG CCAGGTCGGCCACCTCCAC 4504 TGGAGGTGGCCGACCTGGTACCAGGTCGGCCACCTCCA 4505 GGAGGTGGCCGACCTGGTC GACCAGGTCGGCCACCTCC 4506GAGGTGGCCGACCTGGTCA TGACCAGGTCGGCCACCTC 4507 AGGTGGCCGACCTGGTCAGCTGACCAGGTCGGCCACCT 4508 GGTGGCCGACCTGGTCAGC GCTGACCAGGTCGGCCACC 4509GTGGCCGACCTGGTCAGCA TGCTGACCAGGTCGGCCAC 4510 TGGCCGACCTGGTCAGCATATGCTGACCAGGTCGGCCA 4511 GGCCGACCTGGTCAGCATC GATGCTGACCAGGTCGGCC 4512GCCGACCTGGTCAGCATCC GGATGCTGACCAGGTCGGC 4513 CCGACCTGGTCAGCATCCTAGGATGCTGACCAGGTCGG 4514 CGACCTGGTCAGCATCCTG CAGGATGCTGACCAGGTCG 4515GACCTGGTCAGCATCCTGG CCAGGATGCTGACCAGGTC 4516 ACCTGGTCAGCATCCTGGTACCAGGATGCTGACCAGGT 4517 CCTGGTCAGCATCCTGGTG CACCAGGATGCTGACCAGG 4518CTGGTCAGCATCCTGGTGC GCACCAGGATGCTGACCAG 4519 TGGTCAGCATCCTGGTGCATGCACCAGGATGCTGACCA 4520 GGTCAGCATCCTGGTGCAT ATGCACCAGGATGCTGACC 4521GTCAGCATCCTGGTGCATG CATGCACCAGGATGCTGAC 4522 TCAGCATCCTGGTGCATGCGCATGCACCAGGATGCTGA 4523 CAGCATCCTGGTGCATGCC GGCATGCACCAGGATGCTG 4524AGCATCCTGGTGCATGCCG CGGCATGCACCAGGATGCT 4525 GCATCCTGGTGCATGCCGATCGGCATGCACCAGGATGC 4526 CATCCTGGTGCATGCCGAC GTCGGCATGCACCAGGATG 4527ATCCTGGTGCATGCCGACA TGTCGGCATGCACCAGGAT 4528 TCCTGGTGCATGCCGACACGTGTCGGCATGCACCAGGA 4529 CCTGGTGCATGCCGACACA TGTGTCGGCATGCACCAGG 4530CTGGTGCATGCCGACACAC GTGTGTCGGCATGCACCAG 4531 TGGTGCATGCCGACACACCGGTGTGTCGGCATGCACCA 4532 GGTGCATGCCGACACACCA TGGTGTGTCGGCATGCACC 4533GTGCATGCCGACACACCAC GTGGTGTGTCGGCATGCAC 4534 TGCATGCCGACACACCACTAGTGGTGTGTCGGCATGCA 4535 GCATGCCGACACACCACTG CAGTGGTGTGTCGGCATGC 4536CATGCCGACACACCACTGC GCAGTGGTGTGTCGGCATG 4537 ATGCCGACACACCACTGCCGGCAGTGGTGTGTCGGCAT 4538 TGCCGACACACCACTGCCT AGGCAGTGGTGTGTCGGCA 4539GCCGACACACCACTGCCTG CAGGCAGTGGTGTGTCGGC 4540 CCGACACACCACTGCCTGCGCAGGCAGTGGTGTGTCGG 4541 CGACACACCACTGCCTGCC GGCAGGCAGTGGTGTGTCG 4542GACACACCACTGCCTGCCT AGGCAGGCAGTGGTGTGTC 4543 ACACACCACTGCCTGCCTGCAGGCAGGCAGTGGTGTGT 4544 CACACCACTGCCTGCCTGG CCAGGCAGGCAGTGGTGTG 4545ACACCACTGCCTGCCTGGC GCCAGGCAGGCAGTGGTGT 4546 CACCACTGCCTGCCTGGCATGCCAGGCAGGCAGTGGTG 4547 ACCACTGCCTGCCTGGCAC GTGCCAGGCAGGCAGTGGT 4548CCACTGCCTGCCTGGCACC GGTGCCAGGCAGGCAGTGG 4549 CACTGCCTGCCTGGCACCGCGGTGCCAGGCAGGCAGTG 4550 ACTGCCTGCCTGGCACCGG CCGGTGCCAGGCAGGCAGT 4551CTGCCTGCCTGGCACCGGG CCCGGTGCCAGGCAGGCAG 4552 TGCCTGCCTGGCACCGGGCGCCCGGTGCCAGGCAGGCA 4553 GCCTGCCTGGCACCGGGCA TGCCCGGTGCCAGGCAGGC 4554CCTGCCTGGCACCGGGCAC GTGCCCGGTGCCAGGCAGG 4555 CTGCCTGGCACCGGGCACATGTGCCCGGTGCCAGGCAG 4556 TGCCTGGCACCGGGCACAG CTGTGCCCGGTGCCAGGCA 4557GCCTGGCACCGGGCACAGA TCTGTGCCCGGTGCCAGGC 4558 CCTGGCACCGGGCACAGAATTCTGTGCCCGGTGCCAGG 4559 CTGGCACCGGGCACAGAAA TTTCTGTGCCCGGTGCCAG 4560TGGCACCGGGCACAGAAAG CTTTCTGTGCCCGGTGCCA 4561 GGCACCGGGCACAGAAAGATCTTTCTGTGCCCGGTGCC 4562 GCACCGGGCACAGAAAGAC GTCTTTCTGTGCCCGGTGC 4563CACCGGGCACAGAAAGACT AGTCTTTCTGTGCCCGGTG 4564 ACCGGGCACAGAAAGACTTAAGTCTTTCTGTGCCCGGT 4565 CCGGGCACAGAAAGACTTC GAAGTCTTTCTGTGCCCGG 4566CGGGCACAGAAAGACTTCC GGAAGTCTTTCTGTGCCCG 4567 GGGCACAGAAAGACTTCCTAGGAAGTCTTTCTGTGCCC 4568 GGCACAGAAAGACTTCCTT AAGGAAGTCTTTCTGTGCC 4569GCACAGAAAGACTTCCTTT AAAGGAAGTCTTTCTGTGC 4570 CACAGAAAGACTTCCTTTCGAAAGGAAGTCTTTCTGTG 4571 ACAGAAAGACTTCCTTTCA TGAAAGGAAGTCTTTCTGT 4572CAGAAAGACTTCCTTTCAG CTGAAAGGAAGTCTTTCTG 4573 AGAAAGACTTCCTTTCAGGCCTGAAAGGAAGTCTTTCT 4574 GAAAGACTTCCTTTCAGGC GCCTGAAAGGAAGTCTTTC 4575AAAGACTTCCTTTCAGGCC GGCCTGAAAGGAAGTCTTT 4576 AAGACTTCCTTTCAGGCCTAGGCCTGAAAGGAAGTCTT 4577 AGACTTCCTTTCAGGCCTG CAGGCCTGAAAGGAAGTCT 4578GACTTCCTTTCAGGCCTGG CCAGGCCTGAAAGGAAGTC 4579 ACTTCCTTTCAGGCCTGGATCCAGGCCTGAAAGGAAGT 4580 CTTCCTTTCAGGCCTGGAC GTCCAGGCCTGAAAGGAAG 4581TTCCTTTCAGGCCTGGACG CGTCCAGGCCTGAAAGGAA 4582 TCCTTTCAGGCCTGGACGGCCGTCCAGGCCTGAAAGGA 4583 CCTTTCAGGCCTGGACGGG CCCGTCCAGGCCTGAAAGG 4584CTTTCAGGCCTGGACGGGG CCCCGTCCAGGCCTGAAAG 4585 TTTCAGGCCTGGACGGGGATCCCCGTCCAGGCCTGAAA 4586 TTCAGGCCTGGACGGGGAG CTCCCCGTCCAGGCCTGAA 4587TCAGGCCTGGACGGGGAGG CCTCCCCGTCCAGGCCTGA 4588 CAGGCCTGGACGGGGAGGGCCCTCCCCGTCCAGGCCTG 4589 AGGCCTGGACGGGGAGGGG CCCCTCCCCGTCCAGGCCT 4590GGCCTGGACGGGGAGGGGC GCCCCTCCCCGTCCAGGCC 4591 GCCTGGACGGGGAGGGGCTAGCCCCTCCCCGTCCAGGC 4592 CCTGGACGGGGAGGGGCTC GAGCCCCTCCCCGTCCAGG 4593CTGGACGGGGAGGGGCTCT AGAGCCCCTCCCCGTCCAG 4594 TGGACGGGGAGGGGCTCTGCAGAGCCCCTCCCCGTCCA 4595 GGACGGGGAGGGGCTCTGG CCAGAGCCCCTCCCCGTCC 4596GACGGGGAGGGGCTCTGGT ACCAGAGCCCCTCCCCGTC 4597 ACGGGGAGGGGCTCTGGTCGACCAGAGCCCCTCCCCGT 4598 CGGGGAGGGGCTCTGGTCT AGACCAGAGCCCCTCCCCG 4599GGGGAGGGGCTCTGGTCTC GAGACCAGAGCCCCTCCCC 4600 GGGAGGGGCTCTGGTCTCCGGAGACCAGAGCCCCTCCC 4601 GGAGGGGCTCTGGTCTCCG CGGAGACCAGAGCCCCTCC 4602GAGGGGCTCTGGTCTCCGG CCGGAGACCAGAGCCCCTC 4603 AGGGGCTCTGGTCTCCGGGCCCGGAGACCAGAGCCCCT 4604 GGGGCTCTGGTCTCCGGGC GCCCGGAGACCAGAGCCCC 4605GGGCTCTGGTCTCCGGGCA TGCCCGGAGACCAGAGCCC 4606 GGCTCTGGTCTCCGGGCAGCTGCCCGGAGACCAGAGCC 4607 GCTCTGGTCTCCGGGCAGC GCTGCCCGGAGACCAGAGC 4608CTCTGGTCTCCGGGCAGCC GGCTGCCCGGAGACCAGAG 4609 TCTGGTCTCCGGGCAGCCATGGCTGCCCGGAGACCAGA 4610 CTGGTCTCCGGGCAGCCAG CTGGCTGCCCGGAGACCAG 4611TGGTCTCCGGGCAGCCAGG CCTGGCTGCCCGGAGACCA 4612 GGTCTCCGGGCAGCCAGGTACCTGGCTGCCCGGAGACC 4613 GTCTCCGGGCAGCCAGGTC GACCTGGCTGCCCGGAGAC 4614TCTCCGGGCAGCCAGGTCA TGACCTGGCTGCCCGGAGA 4615 CTCCGGGCAGCCAGGTCAGCTGACCTGGCTGCCCGGAG 4616 TCCGGGCAGCCAGGTCAGC GCTGACCTGGCTGCCCGGA 4617CCGGGCAGCCAGGTCAGCA TGCTGACCTGGCTGCCCGG 4618 CGGGCAGCCAGGTCAGCACGTGCTGACCTGGCTGCCCG 4619 GGGCAGCCAGGTCAGCACT AGTGCTGACCTGGCTGCCC 4620GGCAGCCAGGTCAGCACTG CAGTGCTGACCTGGCTGCC 4621 GCAGCCAGGTCAGCACTGTACAGTGCTGACCTGGCTGC 4622 CAGCCAGGTCAGCACTGTG CACAGTGCTGACCTGGCTG 4623AGCCAGGTCAGCACTGTGT ACACAGTGCTGACCTGGCT 4624 GCCAGGTCAGCACTGTGTGCACACAGTGCTGACCTGGC 4625 CCAGGTCAGCACTGTGTGG CCACACAGTGCTGACCTGG 4626CAGGTCAGCACTGTGTGGC GCCACACAGTGCTGACCTG 4627 AGGTCAGCACTGTGTGGCATGCCACACAGTGCTGACCT 4628 GGTCAGCACTGTGTGGCAC GTGCCACACAGTGCTGACC 4629GTCAGCACTGTGTGGCACG CGTGCCACACAGTGCTGAC 4630 TCAGCACTGTGTGGCACGTACGTGCCACACAGTGCTGA 4631 CAGCACTGTGTGGCACGTG CACGTGCCACACAGTGCTG 4632AGCACTGTGTGGCACGTGT ACACGTGCCACACAGTGCT 4633 GCACTGTGTGGCACGTGTTAACACGTGCCACACAGTGC 4634 CACTGTGTGGCACGTGTTC GAACACGTGCCACACAGTG 4635ACTGTGTGGCACGTGTTCC GGAACACGTGCCACACAGT 4636 CTGTGTGGCACGTGTTCCGCGGAACACGTGCCACACAG 4637 TGTGTGGCACGTGTTCCGG CCGGAACACGTGCCACACA 4638GTGTGGCACGTGTTCCGGG CCCGGAACACGTGCCACAC 4639 TGTGGCACGTGTTCCGGGCGCCCGGAACACGTGCCACA 4640 GTGGCACGTGTTCCGGGCA TGCCCGGAACACGTGCCAC 4641TGGCACGTGTTCCGGGCAC GTGCCCGGAACACGTGCCA 4642 GGCACGTGTTCCGGGCACATGTGCCCGGAACACGTGCC 4643 GCACGTGTTCCGGGCACAG CTGTGCCCGGAACACGTGC 4644CACGTGTTCCGGGCACAGG CCTGTGCCCGGAACACGTG 4645 ACGTGTTCCGGGCACAGGATCCTGTGCCCGGAACACGT 4646 CGTGTTCCGGGCACAGGAC GTCCTGTGCCCGGAACACG 4647GTGTTCCGGGCACAGGACG CGTCCTGTGCCCGGAACAC 4648 TGTTCCGGGCACAGGACGCGCGTCCTGTGCCCGGAACA 4649 GTTCCGGGCACAGGACGCC GGCGTCCTGTGCCCGGAAC 4650TTCCGGGCACAGGACGCCC GGGCGTCCTGTGCCCGGAA 4651 TCCGGGCACAGGACGCCCATGGGCGTCCTGTGCCCGGA 4652 CCGGGCACAGGACGCCCAG CTGGGCGTCCTGTGCCCGG 4653CGGGCACAGGACGCCCAGC GCTGGGCGTCCTGTGCCCG 4654 GGGCACAGGACGCCCAGCGCGCTGGGCGTCCTGTGCCC 4655 GGCACAGGACGCCCAGCGC GCGCTGGGCGTCCTGTGCC 4656GCACAGGACGCCCAGCGCA TGCGCTGGGCGTCCTGTGC 4657 CACAGGACGCCCAGCGCATATGCGCTGGGCGTCCTGTG 4658 ACAGGACGCCCAGCGCATC GATGCGCTGGGCGTCCTGT 4659CAGGACGCCCAGCGCATCC GGATGCGCTGGGCGTCCTG 4660 AGGACGCCCAGCGCATCCGCGGATGCGCTGGGCGTCCT 4661 GGACGCCCAGCGCATCCGC GCGGATGCGCTGGGCGTCC 4662GACGCCCAGCGCATCCGCC GGCGGATGCGCTGGGCGTC 4663 ACGCCCAGCGCATCCGCCGCGGCGGATGCGCTGGGCGT 4664 CGCCCAGCGCATCCGCCGC GCGGCGGATGCGCTGGGCG 4665GCCCAGCGCATCCGCCGCT AGCGGCGGATGCGCTGGGC 4666 CCCAGCGCATCCGCCGCTTAAGCGGCGGATGCGCTGGG 4667 CCAGCGCATCCGCCGCTTT AAAGCGGCGGATGCGCTGG 4668CAGCGCATCCGCCGCTTTC GAAAGCGGCGGATGCGCTG 4669 AGCGCATCCGCCGCTTTCTAGAAAGCGGCGGATGCGCT 4670 GCGCATCCGCCGCTTTCTC GAGAAAGCGGCGGATGCGC 4671CGCATCCGCCGCTTTCTCC GGAGAAAGCGGCGGATGCG 4672 GCATCCGCCGCTTTCTCCATGGAGAAAGCGGCGGATGC 4673 CATCCGCCGCTTTCTCCAG CTGGAGAAAGCGGCGGATG 4674ATCCGCCGCTTTCTCCAGA TCTGGAGAAAGCGGCGGAT 4675 TCCGCCGCTTTCTCCAGATATCTGGAGAAAGCGGCGGA 4676 CCGCCGCTTTCTCCAGATG CATCTGGAGAAAGCGGCGG 4677CGCCGCTTTCTCCAGATGG CCATCTGGAGAAAGCGGCG 4678 GCCGCTTTCTCCAGATGGTACCATCTGGAGAAAGCGGC 4679 CCGCTTTCTCCAGATGGTG CACCATCTGGAGAAAGCGG 4680CGCTTTCTCCAGATGGTGT ACACCATCTGGAGAAAGCG 4681 GCTTTCTCCAGATGGTGTGCACACCATCTGGAGAAAGC 4682 CTTTCTCCAGATGGTGTGC GCACACCATCTGGAGAAAG 4683TTTCTCCAGATGGTGTGCC GGCACACCATCTGGAGAAA 4684 TTCTCCAGATGGTGTGCCCGGGCACACCATCTGGAGAA 4685 TCTCCAGATGGTGTGCCCG CGGGCACACCATCTGGAGA 4686CTCCAGATGGTGTGCCCGG CCGGGCACACCATCTGGAG 4687 TCCAGATGGTGTGCCCGGCGCCGGGCACACCATCTGGA 4688 CCAGATGGTGTGCCCGGCC GGCCGGGCACACCATCTGG 4689CAGATGGTGTGCCCGGCCG CGGCCGGGCACACCATCTG 4690 AGATGGTGTGCCCGGCCGGCCGGCCGGGCACACCATCT 4691 GATGGTGTGCCCGGCCGGG CCCGGCCGGGCACACCATC 4692ATGGTGTGCCCGGCCGGGG CCCCGGCCGGGCACACCAT 4693 TGGTGTGCCCGGCCGGGGCGCCCCGGCCGGGCACACCA 4694 GGTGTGCCCGGCCGGGGCA TGCCCCGGCCGGGCACACC 4695GTGTGCCCGGCCGGGGCAG CTGCCCCGGCCGGGCACAC 4696 TGTGCCCGGCCGGGGCAGGCCTGCCCCGGCCGGGCACA 4697 GTGCCCGGCCGGGGCAGGC GCCTGCCCCGGCCGGGCAC 4698TGCCCGGCCGGGGCAGGCG CGCCTGCCCCGGCCGGGCA 4699 GCCCGGCCGGGGCAGGCGCGCGCCTGCCCCGGCCGGGC 4700 CCCGGCCGGGGCAGGCGCC GGCGCCTGCCCCGGCCGGG 4701CCGGCCGGGGCAGGCGCCC GGGCGCCTGCCCCGGCCGG 4702 CGGCCGGGGCAGGCGCCCTAGGGCGCCTGCCCCGGCCG 4703 GGCCGGGGCAGGCGCCCTG CAGGGCGCCTGCCCCGGCC 4704GCCGGGGCAGGCGCCCTGG CCAGGGCGCCTGCCCCGGC 4705 CCGGGGCAGGCGCCCTGGATCCAGGGCGCCTGCCCCGG 4706 CGGGGCAGGCGCCCTGGAG CTCCAGGGCGCCTGCCCCG 4707GGGGCAGGCGCCCTGGAGC GCTCCAGGGCGCCTGCCCC 4708 GGGCAGGCGCCCTGGAGCCGGCTCCAGGGCGCCTGCCC 4709 GGCAGGCGCCCTGGAGCCT AGGCTCCAGGGCGCCTGCC 4710GCAGGCGCCCTGGAGCCTG CAGGCTCCAGGGCGCCTGC 4711 CAGGCGCCCTGGAGCCTGGCCAGGCTCCAGGGCGCCTG 4712 AGGCGCCCTGGAGCCTGGC GCCAGGCTCCAGGGCGCCT 4713GGCGCCCTGGAGCCTGGCG CGCCAGGCTCCAGGGCGCC 4714 GCGCCCTGGAGCCTGGCGCGCGCCAGGCTCCAGGGCGC 4715 CGCCCTGGAGCCTGGCGCC GGCGCCAGGCTCCAGGGCG 4716GCCCTGGAGCCTGGCGCCC GGGCGCCAGGCTCCAGGGC 4717 CCCTGGAGCCTGGCGCCCCGGGGCGCCAGGCTCCAGGG 4718 CCTGGAGCCTGGCGCCCCA TGGGGCGCCAGGCTCCAGG 4719CTGGAGCCTGGCGCCCCAG CTGGGGCGCCAGGCTCCAG 4720 TGGAGCCTGGCGCCCCAGGCCTGGGGCGCCAGGCTCCA 4721 GGAGCCTGGCGCCCCAGGC GCCTGGGGCGCCAGGCTCC 4722GAGCCTGGCGCCCCAGGCA TGCCTGGGGCGCCAGGCTC 4723 AGCCTGGCGCCCCAGGCAGCTGCCTGGGGCGCCAGGCT 4724 GCCTGGCGCCCCAGGCAGC GCTGCCTGGGGCGCCAGGC 4725CCTGGCGCCCCAGGCAGCT AGCTGCCTGGGGCGCCAGG 4726 CTGGCGCCCCAGGCAGCTGCAGCTGCCTGGGGCGCCAG 4727 TGGCGCCCCAGGCAGCTGC GCAGCTGCCTGGGGCGCCA 4728GGCGCCCCAGGCAGCTGCT AGCAGCTGCCTGGGGCGCC 4729 GCGCCCCAGGCAGCTGCTATAGCAGCTGCCTGGGGCGC 4730 CGCCCCAGGCAGCTGCTAC GTAGCAGCTGCCTGGGGCG 4731GCCCCAGGCAGCTGCTACC GGTAGCAGCTGCCTGGGGC 4732 CCCCAGGCAGCTGCTACCTAGGTAGCAGCTGCCTGGGG 4733 CCCAGGCAGCTGCTACCTG CAGGTAGCAGCTGCCTGGG 4734CCAGGCAGCTGCTACCTGG CCAGGTAGCAGCTGCCTGG 4735 CAGGCAGCTGCTACCTGGATCCAGGTAGCAGCTGCCTG 4736 AGGCAGCTGCTACCTGGAT ATCCAGGTAGCAGCTGCCT 4737GGCAGCTGCTACCTGGATG CATCCAGGTAGCAGCTGCC 4738 GCAGCTGCTACCTGGATGCGCATCCAGGTAGCAGCTGC 4739 CAGCTGCTACCTGGATGCA TGCATCCAGGTAGCAGCTG 4740AGCTGCTACCTGGATGCAG CTGCATCCAGGTAGCAGCT 4741 GCTGCTACCTGGATGCAGGCCTGCATCCAGGTAGCAGC 4742 CTGCTACCTGGATGCAGGG CCCTGCATCCAGGTAGCAG 4743TGCTACCTGGATGCAGGGC GCCCTGCATCCAGGTAGCA 4744 GCTACCTGGATGCAGGGCTAGCCCTGCATCCAGGTAGC 4745 CTACCTGGATGCAGGGCTG CAGCCCTGCATCCAGGTAG 4746TACCTGGATGCAGGGCTGC GCAGCCCTGCATCCAGGTA 4747 ACCTGGATGCAGGGCTGCGCGCAGCCCTGCATCCAGGT 4748 CCTGGATGCAGGGCTGCGG CCGCAGCCCTGCATCCAGG 4749CTGGATGCAGGGCTGCGGC GCCGCAGCCCTGCATCCAG 4750 TGGATGCAGGGCTGCGGCGCGCCGCAGCCCTGCATCCA 4751 GGATGCAGGGCTGCGGCGG CCGCCGCAGCCCTGCATCC 4752GATGCAGGGCTGCGGCGGC GCCGCCGCAGCCCTGCATC 4753 ATGCAGGGCTGCGGCGGCGCGCCGCCGCAGCCCTGCAT 4754 TGCAGGGCTGCGGCGGCGC GCGCCGCCGCAGCCCTGCA 4755GCAGGGCTGCGGCGGCGCC GGCGCCGCCGCAGCCCTGC 4756 CAGGGCTGCGGCGGCGCCTAGGCGCCGCCGCAGCCCTG 4757 AGGGCTGCGGCGGCGCCTG CAGGCGCCGCCGCAGCCCT 4758GGGCTGCGGCGGCGCCTGC GCAGGCGCCGCCGCAGCCC 4759 GGCTGCGGCGGCGCCTGCGCGCAGGCGCCGCCGCAGCC 4760 GCTGCGGCGGCGCCTGCGG CCGCAGGCGCCGCCGCAGC 4761CTGCGGCGGCGCCTGCGGG CCCGCAGGCGCCGCCGCAG 4762 TGCGGCGGCGCCTGCGGGATCCCGCAGGCGCCGCCGCA 4763 GCGGCGGCGCCTGCGGGAG CTCCCGCAGGCGCCGCCGC 4764CGGCGGCGCCTGCGGGAGG CCTCCCGCAGGCGCCGCCG 4765 GGCGGCGCCTGCGGGAGGATCCTCCCGCAGGCGCCGCC 4766 GCGGCGCCTGCGGGAGGAG CTCCTCCCGCAGGCGCCGC 4767CGGCGCCTGCGGGAGGAGT ACTCCTCCCGCAGGCGCCG 4768 GGCGCCTGCGGGAGGAGTGCACTCCTCCCGCAGGCGCC 4769 GCGCCTGCGGGAGGAGTGG CCACTCCTCCCGCAGGCGC 4770CGCCTGCGGGAGGAGTGGG CCCACTCCTCCCGCAGGCG 4771 GCCTGCGGGAGGAGTGGGGCCCCACTCCTCCCGCAGGC 4772 CCTGCGGGAGGAGTGGGGC GCCCCACTCCTCCCGCAGG 4773CTGCGGGAGGAGTGGGGCG CGCCCCACTCCTCCCGCAG 4774 TGCGGGAGGAGTGGGGCGTACGCCCCACTCCTCCCGCA 4775 GCGGGAGGAGTGGGGCGTG CACGCCCCACTCCTCCCGC 4776CGGGAGGAGTGGGGCGTGA TCACGCCCCACTCCTCCCG 4777 GGGAGGAGTGGGGCGTGAGCTCACGCCCCACTCCTCCC 4778 GGAGGAGTGGGGCGTGAGC GCTCACGCCCCACTCCTCC 4779GAGGAGTGGGGCGTGAGCT AGCTCACGCCCCACTCCTC 4780 AGGAGTGGGGCGTGAGCTGCAGCTCACGCCCCACTCCT 4781 GGAGTGGGGCGTGAGCTGC GCAGCTCACGCCCCACTCC 4782GAGTGGGGCGTGAGCTGCT AGCAGCTCACGCCCCACTC 4783 AGTGGGGCGTGAGCTGCTGCAGCAGCTCACGCCCCACT 4784 GTGGGGCGTGAGCTGCTGG CCAGCAGCTCACGCCCCAC 4785TGGGGCGTGAGCTGCTGGA TCCAGCAGCTCACGCCCCA 4786 GGGGCGTGAGCTGCTGGACGTCCAGCAGCTCACGCCCC 4787 GGGCGTGAGCTGCTGGACC GGTCCAGCAGCTCACGCCC 4788GGCGTGAGCTGCTGGACCC GGGTCCAGCAGCTCACGCC 4789 GCGTGAGCTGCTGGACCCTAGGGTCCAGCAGCTCACGC 4790 CGTGAGCTGCTGGACCCTG CAGGGTCCAGCAGCTCACG 4791GTGAGCTGCTGGACCCTGC GCAGGGTCCAGCAGCTCAC 4792 TGAGCTGCTGGACCCTGCTAGCAGGGTCCAGCAGCTCA 4793 GAGCTGCTGGACCCTGCTC GAGCAGGGTCCAGCAGCTC 4794AGCTGCTGGACCCTGCTCC GGAGCAGGGTCCAGCAGCT 4795 GCTGCTGGACCCTGCTCCATGGAGCAGGGTCCAGCAGC 4796 CTGCTGGACCCTGCTCCAG CTGGAGCAGGGTCCAGCAG 4797TGCTGGACCCTGCTCCAGG CCTGGAGCAGGGTCCAGCA 4798 GCTGGACCCTGCTCCAGGCGCCTGGAGCAGGGTCCAGC 4799 CTGGACCCTGCTCCAGGCC GGCCTGGAGCAGGGTCCAG 4800TGGACCCTGCTCCAGGCCC GGGCCTGGAGCAGGGTCCA 4801 GGACCCTGCTCCAGGCCCCGGGGCCTGGAGCAGGGTCC 4802 GACCCTGCTCCAGGCCCCC GGGGGCCTGGAGCAGGGTC 4803ACCCTGCTCCAGGCCCCCG CGGGGGCCTGGAGCAGGGT 4804 CCCTGCTCCAGGCCCCCGGCCGGGGGCCTGGAGCAGGG 4805 CCTGCTCCAGGCCCCCGGA TCCGGGGGCCTGGAGCAGG 4806CTGCTCCAGGCCCCCGGAG CTCCGGGGGCCTGGAGCAG 4807 TGCTCCAGGCCCCCGGAGATCTCCGGGGGCCTGGAGCA 4808 GCTCCAGGCCCCCGGAGAG CTCTCCGGGGGCCTGGAGC 4809CTCCAGGCCCCCGGAGAGG CCTCTCCGGGGGCCTGGAG 4810 TCCAGGCCCCCGGAGAGGCGCCTCTCCGGGGGCCTGGA 4811 CCAGGCCCCCGGAGAGGCC GGCCTCTCCGGGGGCCTGG 4812CAGGCCCCCGGAGAGGCCG CGGCCTCTCCGGGGGCCTG 4813 AGGCCCCCGGAGAGGCCGTACGGCCTCTCCGGGGGCCT 4814 GGCCCCCGGAGAGGCCGTG CACGGCCTCTCCGGGGGCC 4815GCCCCCGGAGAGGCCGTGC GCACGGCCTCTCCGGGGGC 4816 CCCCCGGAGAGGCCGTGCTAGCACGGCCTCTCCGGGGG 4817 CCCCGGAGAGGCCGTGCTG CAGCACGGCCTCTCCGGGG 4818CCCGGAGAGGCCGTGCTGG CCAGCACGGCCTCTCCGGG 4819 CCGGAGAGGCCGTGCTGGTACCAGCACGGCCTCTCCGG 4820 CGGAGAGGCCGTGCTGGTG CACCAGCACGGCCTCTCCG 4821GGAGAGGCCGTGCTGGTGC GCACCAGCACGGCCTCTCC 4822 GAGAGGCCGTGCTGGTGCCGGCACCAGCACGGCCTCTC 4823 AGAGGCCGTGCTGGTGCCT AGGCACCAGCACGGCCTCT 4824GAGGCCGTGCTGGTGCCTG CAGGCACCAGCACGGCCTC 4825 AGGCCGTGCTGGTGCCTGCGCAGGCACCAGCACGGCCT 4826 GGCCGTGCTGGTGCCTGCA TGCAGGCACCAGCACGGCC 4827GCCGTGCTGGTGCCTGCAG CTGCAGGCACCAGCACGGC 4828 CCGTGCTGGTGCCTGCAGGCCTGCAGGCACCAGCACGG 4829 CGTGCTGGTGCCTGCAGGG CCCTGCAGGCACCAGCACG 4830GTGCTGGTGCCTGCAGGGG CCCCTGCAGGCACCAGCAC 4831 TGCTGGTGCCTGCAGGGGCGCCCCTGCAGGCACCAGCA 4832 GCTGGTGCCTGCAGGGGCT AGCCCCTGCAGGCACCAGC 4833CTGGTGCCTGCAGGGGCTC GAGCCCCTGCAGGCACCAG 4834 TGGTGCCTGCAGGGGCTCCGGAGCCCCTGCAGGCACCA 4835 GGTGCCTGCAGGGGCTCCC GGGAGCCCCTGCAGGCACC 4836GTGCCTGCAGGGGCTCCCC GGGGAGCCCCTGCAGGCAC 4837 TGCCTGCAGGGGCTCCCCATGGGGAGCCCCTGCAGGCA 4838 GCCTGCAGGGGCTCCCCAC GTGGGGAGCCCCTGCAGGC 4839CCTGCAGGGGCTCCCCACC GGTGGGGAGCCCCTGCAGG 4840 CTGCAGGGGCTCCCCACCATGGTGGGGAGCCCCTGCAG 4841 TGCAGGGGCTCCCCACCAG CTGGTGGGGAGCCCCTGCA 4842GCAGGGGCTCCCCACCAGG CCTGGTGGGGAGCCCCTGC 4843 CAGGGGCTCCCCACCAGGTACCTGGTGGGGAGCCCCTG 4844 AGGGGCTCCCCACCAGGTG CACCTGGTGGGGAGCCCCT 4845GGGGCTCCCCACCAGGTGC GCACCTGGTGGGGAGCCCC 4846 GGGCTCCCCACCAGGTGCATGCACCTGGTGGGGAGCCC 4847 GGCTCCCCACCAGGTGCAG CTGCACCTGGTGGGGAGCC 4848GCTCCCCACCAGGTGCAGG CCTGCACCTGGTGGGGAGC 4849 CTCCCCACCAGGTGCAGGGCCCTGCACCTGGTGGGGAG 4850 TCCCCACCAGGTGCAGGGC GCCCTGCACCTGGTGGGGA 4851CCCCACCAGGTGCAGGGCC GGCCCTGCACCTGGTGGGG 4852 CCCACCAGGTGCAGGGCCTAGGCCCTGCACCTGGTGGG 4853 CCACCAGGTGCAGGGCCTG CAGGCCCTGCACCTGGTGG 4854CACCAGGTGCAGGGCCTGG CCAGGCCCTGCACCTGGTG 4855 ACCAGGTGCAGGGCCTGGTACCAGGCCCTGCACCTGGT 4856 CCAGGTGCAGGGCCTGGTG CACCAGGCCCTGCACCTGG 4857CAGGTGCAGGGCCTGGTGA TCACCAGGCCCTGCACCTG 4858 AGGTGCAGGGCCTGGTGAGCTCACCAGGCCCTGCACCT 4859 GGTGCAGGGCCTGGTGAGC GCTCACCAGGCCCTGCACC 4860GTGCAGGGCCTGGTGAGCA TGCTCACCAGGCCCTGCAC 4861 TGCAGGGCCTGGTGAGCACGTGCTCACCAGGCCCTGCA 4862 GCAGGGCCTGGTGAGCACA TGTGCTCACCAGGCCCTGC 4863CAGGGCCTGGTGAGCACAG CTGTGCTCACCAGGCCCTG 4864 AGGGCCTGGTGAGCACAGTACTGTGCTCACCAGGCCCT 4865 GGGCCTGGTGAGCACAGTC GACTGTGCTCACCAGGCCC 4866GGCCTGGTGAGCACAGTCA TGACTGTGCTCACCAGGCC 4867 GCCTGGTGAGCACAGTCAGCTGACTGTGCTCACCAGGC 4868 CCTGGTGAGCACAGTCAGC GCTGACTGTGCTCACCAGG 4869CTGGTGAGCACAGTCAGCG CGCTGACTGTGCTCACCAG 4870 TGGTGAGCACAGTCAGCGTACGCTGACTGTGCTCACCA 4871 GGTGAGCACAGTCAGCGTC GACGCTGACTGTGCTCACC 4872GTGAGCACAGTCAGCGTCA TGACGCTGACTGTGCTCAC 4873 TGAGCACAGTCAGCGTCACGTGACGCTGACTGTGCTCA 4874 GAGCACAGTCAGCGTCACT AGTGACGCTGACTGTGCTC 4875AGCACAGTCAGCGTCACTC GAGTGACGCTGACTGTGCT 4876 GCACAGTCAGCGTCACTCATGAGTGACGCTGACTGTGC 4877 CACAGTCAGCGTCACTCAG CTGAGTGACGCTGACTGTG 4878ACAGTCAGCGTCACTCAGC GCTGAGTGACGCTGACTGT 4879 CAGTCAGCGTCACTCAGCATGCTGAGTGACGCTGACTG 4880 AGTCAGCGTCACTCAGCAC GTGCTGAGTGACGCTGACT 4881GTCAGCGTCACTCAGCACT AGTGCTGAGTGACGCTGAC 4882 TCAGCGTCACTCAGCACTTAAGTGCTGAGTGACGCTGA 4883 CAGCGTCACTCAGCACTTC GAAGTGCTGAGTGACGCTG 4884AGCGTCACTCAGCACTTCC GGAAGTGCTGAGTGACGCT 4885 GCGTCACTCAGCACTTCCTAGGAAGTGCTGAGTGACGC 4886 CGTCACTCAGCACTTCCTC GAGGAAGTGCTGAGTGACG 4887GTCACTCAGCACTTCCTCT AGAGGAAGTGCTGAGTGAC 4888 TCACTCAGCACTTCCTCTCGAGAGGAAGTGCTGAGTGA 4889 CACTCAGCACTTCCTCTCC GGAGAGGAAGTGCTGAGTG 4890ACTCAGCACTTCCTCTCCC GGGAGAGGAAGTGCTGAGT 4891 CTCAGCACTTCCTCTCCCCGGGGAGAGGAAGTGCTGAG 4892 TCAGCACTTCCTCTCCCCT AGGGGAGAGGAAGTGCTGA 4893CAGCACTTCCTCTCCCCTG CAGGGGAGAGGAAGTGCTG 4894 AGCACTTCCTCTCCCCTGATCAGGGGAGAGGAAGTGCT 4895 GCACTTCCTCTCCCCTGAG CTCAGGGGAGAGGAAGTGC 4896CACTTCCTCTCCCCTGAGA TCTCAGGGGAGAGGAAGTG 4897 ACTTCCTCTCCCCTGAGACGTCTCAGGGGAGAGGAAGT 4898 CTTCCTCTCCCCTGAGACC GGTCTCAGGGGAGAGGAAG 4899TTCCTCTCCCCTGAGACCT AGGTCTCAGGGGAGAGGAA 4900 TCCTCTCCCCTGAGACCTCGAGGTCTCAGGGGAGAGGA 4901 CCTCTCCCCTGAGACCTCT AGAGGTCTCAGGGGAGAGG 4902CTCTCCCCTGAGACCTCTG CAGAGGTCTCAGGGGAGAG 4903 TCTCCCCTGAGACCTCTGCGCAGAGGTCTCAGGGGAGA 4904 CTCCCCTGAGACCTCTGCC GGCAGAGGTCTCAGGGGAG 4905TCCCCTGAGACCTCTGCCC GGGCAGAGGTCTCAGGGGA 4906 CCCCTGAGACCTCTGCCCTAGGGCAGAGGTCTCAGGGG 4907 CCCTGAGACCTCTGCCCTC GAGGGCAGAGGTCTCAGGG 4908CCTGAGACCTCTGCCCTCT AGAGGGCAGAGGTCTCAGG 4909 CTGAGACCTCTGCCCTCTCGAGAGGGCAGAGGTCTCAG 4910 TGAGACCTCTGCCCTCTCT AGAGAGGGCAGAGGTCTCA 4911GAGACCTCTGCCCTCTCTG CAGAGAGGGCAGAGGTCTC 4912 AGACCTCTGCCCTCTCTGCGCAGAGAGGGCAGAGGTCT 4913 GACCTCTGCCCTCTCTGCT AGCAGAGAGGGCAGAGGTC 4914ACCTCTGCCCTCTCTGCTC GAGCAGAGAGGGCAGAGGT 4915 CCTCTGCCCTCTCTGCTCATGAGCAGAGAGGGCAGAGG 4916 CTCTGCCCTCTCTGCTCAG CTGAGCAGAGAGGGCAGAG 4917TCTGCCCTCTCTGCTCAGC GCTGAGCAGAGAGGGCAGA 4918 CTGCCCTCTCTGCTCAGCTAGCTGAGCAGAGAGGGCAG 4919 TGCCCTCTCTGCTCAGCTC GAGCTGAGCAGAGAGGGCA 4920GCCCTCTCTGCTCAGCTCT AGAGCTGAGCAGAGAGGGC 4921 CCCTCTCTGCTCAGCTCTGCAGAGCTGAGCAGAGAGGG 4922 CCTCTCTGCTCAGCTCTGC GCAGAGCTGAGCAGAGAGG 4923CTCTCTGCTCAGCTCTGCC GGCAGAGCTGAGCAGAGAG 4924 TCTCTGCTCAGCTCTGCCATGGCAGAGCTGAGCAGAGA 4925 CTCTGCTCAGCTCTGCCAC GTGGCAGAGCTGAGCAGAG 4926TCTGCTCAGCTCTGCCACC GGTGGCAGAGCTGAGCAGA 4927 CTGCTCAGCTCTGCCACCATGGTGGCAGAGCTGAGCAG 4928 TGCTCAGCTCTGCCACCAG CTGGTGGCAGAGCTGAGCA 4929GCTCAGCTCTGCCACCAGG CCTGGTGGCAGAGCTGAGC 4930 CTCAGCTCTGCCACCAGGGCCCTGGTGGCAGAGCTGAG 4931 TCAGCTCTGCCACCAGGGA TCCCTGGTGGCAGAGCTGA 4932CAGCTCTGCCACCAGGGAC GTCCCTGGTGGCAGAGCTG 4933 AGCTCTGCCACCAGGGACCGGTCCCTGGTGGCAGAGCT 4934 GCTCTGCCACCAGGGACCC GGGTCCCTGGTGGCAGAGC 4935CTCTGCCACCAGGGACCCA TGGGTCCCTGGTGGCAGAG 4936 TCTGCCACCAGGGACCCAGCTGGGTCCCTGGTGGCAGA 4937 CTGCCACCAGGGACCCAGC GCTGGGTCCCTGGTGGCAG 4938TGCCACCAGGGACCCAGCC GGCTGGGTCCCTGGTGGCA 4939 GCCACCAGGGACCCAGCCTAGGCTGGGTCCCTGGTGGC 4940 CCACCAGGGACCCAGCCTT AAGGCTGGGTCCCTGGTGG 4941CACCAGGGACCCAGCCTTC GAAGGCTGGGTCCCTGGTG 4942 ACCAGGGACCCAGCCTTCCGGAAGGCTGGGTCCCTGGT 4943 CCAGGGACCCAGCCTTCCC GGGAAGGCTGGGTCCCTGG 4944CAGGGACCCAGCCTTCCCC GGGGAAGGCTGGGTCCCTG 4945 AGGGACCCAGCCTTCCCCCGGGGGAAGGCTGGGTCCCT 4946 GGGACCCAGCCTTCCCCCT AGGGGGAAGGCTGGGTCCC 4947GGACCCAGCCTTCCCCCTG CAGGGGGAAGGCTGGGTCC 4948 GACCCAGCCTTCCCCCTGATCAGGGGGAAGGCTGGGTC 4949 ACCCAGCCTTCCCCCTGAC GTCAGGGGGAAGGCTGGGT 4950CCCAGCCTTCCCCCTGACT AGTCAGGGGGAAGGCTGGG 4951 CCAGCCTTCCCCCTGACTGCAGTCAGGGGGAAGGCTGG 4952 CAGCCTTCCCCCTGACTGC GCAGTCAGGGGGAAGGCTG 4953AGCCTTCCCCCTGACTGCC GGCAGTCAGGGGGAAGGCT 4954 GCCTTCCCCCTGACTGCCATGGCAGTCAGGGGGAAGGC 4955 CCTTCCCCCTGACTGCCAC GTGGCAGTCAGGGGGAAGG 4956CTTCCCCCTGACTGCCACC GGTGGCAGTCAGGGGGAAG 4957 TTCCCCCTGACTGCCACCTAGGTGGCAGTCAGGGGGAA 4958 TCCCCCTGACTGCCACCTG CAGGTGGCAGTCAGGGGGA 4959CCCCCTGACTGCCACCTGC GCAGGTGGCAGTCAGGGGG 4960 CCCCTGACTGCCACCTGCTAGCAGGTGGCAGTCAGGGG 4961 CCCTGACTGCCACCTGCTT AAGCAGGTGGCAGTCAGGG 4962CCTGACTGCCACCTGCTTT AAAGCAGGTGGCAGTCAGG 4963 CTGACTGCCACCTGCTTTATAAAGCAGGTGGCAGTCAG 4964 TGACTGCCACCTGCTTTAT ATAAAGCAGGTGGCAGTCA 4965GACTGCCACCTGCTTTATG CATAAAGCAGGTGGCAGTC 4966 ACTGCCACCTGCTTTATGCGCATAAAGCAGGTGGCAGT 4967 CTGCCACCTGCTTTATGCC GGCATAAAGCAGGTGGCAG 4968TGCCACCTGCTTTATGCCC GGGCATAAAGCAGGTGGCA 4969 GCCACCTGCTTTATGCCCATGGGCATAAAGCAGGTGGC 4970 CCACCTGCTTTATGCCCAG CTGGGCATAAAGCAGGTGG 4971CACCTGCTTTATGCCCAGA TCTGGGCATAAAGCAGGTG 4972 ACCTGCTTTATGCCCAGATATCTGGGCATAAAGCAGGT 4973 CCTGCTTTATGCCCAGATG CATCTGGGCATAAAGCAGG 4974CTGCTTTATGCCCAGATGG CCATCTGGGCATAAAGCAG 4975 TGCTTTATGCCCAGATGGATCCATCTGGGCATAAAGCA 4976 GCTTTATGCCCAGATGGAC GTCCATCTGGGCATAAAGC 4977CTTTATGCCCAGATGGACT AGTCCATCTGGGCATAAAG 4978 TTTATGCCCAGATGGACTGCAGTCCATCTGGGCATAAA 4979 TTATGCCCAGATGGACTGG CCAGTCCATCTGGGCATAA 4980TATGCCCAGATGGACTGGG CCCAGTCCATCTGGGCATA 4981 ATGCCCAGATGGACTGGGCGCCCAGTCCATCTGGGCAT 4982 TGCCCAGATGGACTGGGCT AGCCCAGTCCATCTGGGCA 4983GCCCAGATGGACTGGGCTG CAGCCCAGTCCATCTGGGC 4984 CCCAGATGGACTGGGCTGTACAGCCCAGTCCATCTGGG 4985 CCAGATGGACTGGGCTGTG CACAGCCCAGTCCATCTGG 4986CAGATGGACTGGGCTGTGT ACACAGCCCAGTCCATCTG 4987 AGATGGACTGGGCTGTGTTAACACAGCCCAGTCCATCT 4988 GATGGACTGGGCTGTGTTC GAACACAGCCCAGTCCATC 4989ATGGACTGGGCTGTGTTCC GGAACACAGCCCAGTCCAT 4990 TGGACTGGGCTGTGTTCCATGGAACACAGCCCAGTCCA 4991 GGACTGGGCTGTGTTCCAA TTGGAACACAGCCCAGTCC 4992GACTGGGCTGTGTTCCAAG CTTGGAACACAGCCCAGTC 4993 ACTGGGCTGTGTTCCAAGCGCTTGGAACACAGCCCAGT 4994 CTGGGCTGTGTTCCAAGCA TGCTTGGAACACAGCCCAG 4995TGGGCTGTGTTCCAAGCAG CTGCTTGGAACACAGCCCA 4996 GGGCTGTGTTCCAAGCAGTACTGCTTGGAACACAGCCC 4997 GGCTGTGTTCCAAGCAGTG CACTGCTTGGAACACAGCC 4998GCTGTGTTCCAAGCAGTGA TCACTGCTTGGAACACAGC 4999 CTGTGTTCCAAGCAGTGAATTCACTGCTTGGAACACAG 5000 TGTGTTCCAAGCAGTGAAG CTTCACTGCTTGGAACACA 5001GTGTTCCAAGCAGTGAAGG CCTTCACTGCTTGGAACAC 5002 TGTTCCAAGCAGTGAAGGTACCTTCACTGCTTGGAACA 5003 GTTCCAAGCAGTGAAGGTG CACCTTCACTGCTTGGAAC 5004TTCCAAGCAGTGAAGGTGG CCACCTTCACTGCTTGGAA 5005 TCCAAGCAGTGAAGGTGGCGCCACCTTCACTGCTTGGA 5006 CCAAGCAGTGAAGGTGGCC GGCCACCTTCACTGCTTGG 5007CAAGCAGTGAAGGTGGCCG CGGCCACCTTCACTGCTTG 5008 AAGCAGTGAAGGTGGCCGTACGGCCACCTTCACTGCTT 5009 AGCAGTGAAGGTGGCCGTG CACGGCCACCTTCACTGCT 5010GCAGTGAAGGTGGCCGTGG CCACGGCCACCTTCACTGC 5011 CAGTGAAGGTGGCCGTGGGCCCACGGCCACCTTCACTG 5012 AGTGAAGGTGGCCGTGGGG CCCCACGGCCACCTTCACT 5013GTGAAGGTGGCCGTGGGGA TCCCCACGGCCACCTTCAC 5014 TGAAGGTGGCCGTGGGGACGTCCCCACGGCCACCTTCA 5015 GAAGGTGGCCGTGGGGACA TGTCCCCACGGCCACCTTC 5016AAGGTGGCCGTGGGGACAT ATGTCCCCACGGCCACCTT 5017 AGGTGGCCGTGGGGACATTAATGTCCCCACGGCCACCT 5018 GGTGGCCGTGGGGACATTA TAATGTCCCCACGGCCACC 5019GTGGCCGTGGGGACATTAC GTAATGTCCCCACGGCCAC 5020 TGGCCGTGGGGACATTACATGTAATGTCCCCACGGCCA 5021 GGCCGTGGGGACATTACAG CTGTAATGTCCCCACGGCC 5022GCCGTGGGGACATTACAGG CCTGTAATGTCCCCACGGC 5023 CCGTGGGGACATTACAGGATCCTGTAATGTCCCCACGG 5024 CGTGGGGACATTACAGGAG CTCCTGTAATGTCCCCACG 5025GTGGGGACATTACAGGAGG CCTCCTGTAATGTCCCCAC 5026 TGGGGACATTACAGGAGGCGCCTCCTGTAATGTCCCCA 5027 GGGGACATTACAGGAGGCC GGCCTCCTGTAATGTCCCC 5028GGGACATTACAGGAGGCCA TGGCCTCCTGTAATGTCCC 5029 GGACATTACAGGAGGCCAATTGGCCTCCTGTAATGTCC 5030 GACATTACAGGAGGCCAAA TTTGGCCTCCTGTAATGTC 5031ACATTACAGGAGGCCAAAT ATTTGGCCTCCTGTAATGT 5032 CATTACAGGAGGCCAAATATATTTGGCCTCCTGTAATG 5033 ATTACAGGAGGCCAAATAG CTATTTGGCCTCCTGTAAT 5034TTACAGGAGGCCAAATAGA TCTATTTGGCCTCCTGTAA 5035 TACAGGAGGCCAAATAGAGCTCTATTTGGCCTCGTGTA 5036 ACAGGAGGCCAAATAGAGG CCTCTATTTGGCCTCCTGT 5037CAGGAGGCCAAATAGAGGG CCCTCTATTTGGCCTCCTG 5038 AGGAGGCCAAATAGAGGGATCCCTCTATTTGGCCTCCT 5039 GGAGGCCAAATAGAGGGAT ATCCCTCTATTTGGCCTCC 5040GAGGCCAAATAGAGGGATG CATCCCTCTATTTGGCCTC 5041 AGGCCAAATAGAGGGATGCGCATCCCTCTATTTGGCCT 5042 GGCCAAATAGAGGGATGCT AGCATCCCTCTATTTGGCC 5043GCCAAATAGAGGGATGCTA TAGCATCCCTCTATTTGGC 5044 CCAAATAGAGGGATGCTAGCTAGCATCCCTCTATTTGG 5045 CAAATAGAGGGATGCTAGG CCTAGCATCCCTCTATTTG 5046AAATAGAGGGATGCTAGGT ACCTAGCATCCCTCTATTT 5047 AATAGAGGGATGCTAGGTGCACCTAGCATCCCTCTATT 5048 ATAGAGGGATGCTAGGTGT ACACCTAGCATCCCTCTAT 5049TAGAGGGATGCTAGGTGTC GACACCTAGCATCCCTCTA 5050 AGAGGGATGCTAGGTGTCTAGACACCTAGCATCCCTCT 5051 GAGGGATGCTAGGTGTCTG CAGACACCTAGCATCCCTC 5052AGGGATGCTAGGTGTCTGG CCAGACACCTAGCATCCCT 5053 GGGATGCTAGGTGTCTGGGCCCAGACACCTAGCATCCC 5054 GGATGCTAGGTGTCTGGGA TCCCAGACACCTAGCATCC 5055GATGCTAGGTGTCTGGGAT ATCCCAGACACCTAGCATC 5056 ATGCTAGGTGTCTGGGATCGATCCCAGACACCTAGCAT 5057 TGCTAGGTGTCTGGGATCG CGATCCCAGACACCTAGCA 5058GCTAGGTGTCTGGGATCGG CCGATCCCAGACACCTAGC 5059 CTAGGTGTCTGGGATCGGGCCCGATCCCAGACACCTAG 5060 TAGGTGTCTGGGATCGGGG CCCCGATCCCAGACACCTA 5061AGGTGTCTGGGATCGGGGT ACCCCGATCCCAGACACCT 5062 GGTGTCTGGGATCGGGGTGCACCCCGATCCCAGACACC 5063 GTGTCTGGGATCGGGGTGG CCACCCCGATCCCAGACAC 5064TGTCTGGGATCGGGGTGGG CCCACCCCGATCCCAGACA 5065 GTCTGGGATCGGGGTGGGGCCCCACCCCGATCCCAGAC 5066 TCTGGGATCGGGGTGGGGA TCCCCACCCCGATCCCAGA 5067CTGGGATCGGGGTGGGGAC GTCCCCACCCCGATCCCAG 5068 TGGGATCGGGGTGGGGACATGTCCCCACCCCGATCCCA 5069 GGGATCGGGGTGGGGACAG CTGTCCCCACCCCGATCCC 5070GGATCGGGGTGGGGACAGG CCTGTCCCCACCCCGATCC 5071 GATCGGGGTGGGGACAGGTACCTGTCCCCACCCCGATC 5072 ATCGGGGTGGGGACAGGTA TACCTGTCCCCACCCCGAT 5073TCGGGGTGGGGACAGGTAG CTACCTGTCCCCACCCCGA 5074 CGGGGTGGGGACAGGTAGATCTACCTGTCCCCACCCCG 5075 GGGGTGGGGACAGGTAGAC GTCTACCTGTCCCCACCCC 5076GGGTGGGGACAGGTAGACC GGTCTACCTGTCCCCACCC 5077 GGTGGGGACAGGTAGACCATGGTCTACCTGTCCCCACC 5078 GTGGGGACAGGTAGACCAG CTGGTCTACCTGTCCCCAC 5079TGGGGACAGGTAGACCAGG CCTGGTCTACCTGTCCCCA 5080 GGGGACAGGTAGACCAGGTACCTGGTCTACCTGTCCCC 5081 GGGACAGGTAGACCAGGTG CACCTGGTCTACCTGTCCC 5082GGACAGGTAGACCAGGTGC GCACCTGGTCTACCTGTCC 5083 GACAGGTAGACCAGGTGCTAGCACCTGGTCTACCTGTC 5084 ACAGGTAGACCAGGTGCTC GAGCACCTGGTCTACCTGT 5085CAGGTAGACCAGGTGCTCA TGAGCACCTGGTCTACCTG 5086 AGGTAGACCAGGTGCTCAGCTGAGCACCTGGTCTACCT 5087 GGTAGACCAGGTGCTCAGC GCTGAGCACCTGGTCTACC 5088GTAGACCAGGTGCTCAGCC GGCTGAGCACCTGGTCTAC 5089 TAGACCAGGTGCTCAGCCCGGGCTGAGCACCTGGTCTA 5090 AGACCAGGTGCTCAGCCCA TGGGCTGAGCACCTGGTCT 5091GACCAGGTGCTCAGCCCAG CTGGGCTGAGCACCTGGTC 5092 ACCAGGTGCTCAGCCCAGGCCTGGGCTGAGCACCTGGT 5093 CCAGGTGCTCAGCCCAGGC GCCTGGGCTGAGCACCTGG 5094CAGGTGCTCAGCCCAGGCA TGCCTGGGCTGAGCACCTG 5095 AGGTGCTCAGCCCAGGCACGTGCCTGGGCTGAGCACCT 5096 GGTGCTCAGCCCAGGCACA TGTGCCTGGGCTGAGCACC 5097GTGCTCAGCCCAGGCACAA TTGTGCCTGGGCTGAGCAC 5098 TGCTCAGCCCAGGCACAACGTTGTGCCTGGGCTGAGCA 5099 GCTCAGCCCAGGCACAACT AGTTGTGCCTGGGCTGAGC 5100CTCAGCCCAGGCACAACTT AAGTTGTGCCTGGGCTGAG 5101 TCAGCCCAGGCACAACTTCGAAGTTGTGCCTGGGCTGA 5102 CAGCCCAGGCACAACTTCA TGAAGTTGTGCCTGGGCTG 5103AGCCCAGGCACAACTTCAG CTGAAGTTGTGCCTGGGCT 5104 GCCCAGGCACAACTTCAGCGCTGAAGTTGTGCCTGGGC 5105 CCCAGGCACAACTTCAGCA TGCTGAAGTTGTGCCTGGG 5106CCAGGCACAACTTCAGCAG CTGCTGAAGTTGTGCCTGG 5107 CAGGCACAACTTCAGCAGGCCTGCTGAAGTTGTGCCTG 5108 AGGCACAACTTCAGCAGGG CCCTGCTGAAGTTGTGCCT 5109GGCACAACTTCAGCAGGGG CCCCTGCTGAAGTTGTGCC 5110 GCACAACTTCAGCAGGGGATCCCCTGCTGAAGTTGTGC 5111 GACAACTTCAGCAGGGGAT ATCCCCTGCTGAAGTTGTG 5112ACAACTTCAGCAGGGGATG CATCCCCTGCTGAAGTTGT 5113 CAACTTCAGCAGGGGATGGCCATCCCCTGCTGAAGTTG 5114 AACTTCAGCAGGGGATGGC GCCATCCCCTGCTGAAGTT 5115ACTTCAGCAGGGGATGGCG CGCCATCCCCTGCTGAAGT 5116 CTTCAGCAGGGGATGGCGCGCGCCATCCCCTGCTGAAG 5117 TTCAGCAGGGGATGGCGCT AGCGCCATCCCCTGCTGAA 5118TCAGCAGGGGATGGCGCTA TAGCGCCATCCCCTGCTGA 5119 CAGCAGGGGATGGCGCTAGCTAGCGCCATCCCCTGCTG 5120 AGCAGGGGATGGCGCTAGG CCTAGCGCCATCCCCTGCT 5121GCAGGGGATGGCGCTAGGG CCCTAGCGCCATCCCCTGC 5122 CAGGGGATGGCGCTAGGGGCCCCTAGCGCCATCCCCTG 5123 AGGGGATGGCGCTAGGGGA TCCCCTAGCGCCATCCCCT 5124GGGGATGGCGCTAGGGGAC GTCCCCTAGCGCCATCCCC 5125 GGGATGGCGCTAGGGGACTAGTCCCCTAGCGCCATCCC 5126 GGATGGCGCTAGGGGACTT AAGTCCCCTAGCGCCATCC 5127GATGGCGCTAGGGGACTTG CAAGTCCCCTAGCGCCATC 5128 ATGGCGCTAGGGGACTTGGCCAAGTCCCCTAGCGCCAT 5129 TGGCGCTAGGGGACTTGGG CCCAAGTCCCCTAGCGCCA 5130GGCGCTAGGGGACTTGGGG CCCCAAGTCCCCTAGCGCC 5131 GCGCTAGGGGACTTGGGGATCCCCAAGTCCCCTAGCGC 5132 CGCTAGGGGACTTGGGGAT ATCCCCAAGTCCCCTAGCG 5133GCTAGGGGACTTGGGGATT AATCCCCAAGTCCCCTAGC 5134 CTAGGGGACTTGGGGATTTAAATCCCCAAGTCCCCTAG 5135 TAGGGGACTTGGGGATTTC GAAATCCCCAAGTCCCCTA 5136AGGGGACTTGGGGATTTCT AGAAATCCCCAAGTCCCCT 5137 GGGGACTTGGGGATTTCTGCAGAAATCCCCAAGTCCCC 5138 GGGACTTGGGGATTTCTGG CCAGAAATCCCCAAGTCCC 5139GGACTTGGGGATTTCTGGT ACCAGAAATCCCCAAGTCC 5140 GACTTGGGGATTTCTGGTCGACCAGAAATCCCCAAGTC 5141 ACTTGGGGATTTCTGGTCA TGACCAGAAATCCCCAAGT 5142CTTGGGGATTTCTGGTCAA TTGACCAGAAATCCCCAAG 5143 TTGGGGATTTCTGGTCAACGTTGACCAGAAATCCCCAA 5144 TGGGGATTTCTGGTCAACC GGTTGACCAGAAATCCCCA 5145GGGGATTTCTGGTCAACCC GGGTTGACCAGAAATCCCC 5146 GGGATTTCTGGTCAACCCCGGGGTTGACCAGAAATCCC 5147 GGATTTCTGGTCAACCCCA TGGGGTTGACCAGAAATCC 5148GATTTCTGGTCAACCCCAC GTGGGGTTGACCAGAAATC 5149 ATTTCTGGTCAACCCCACATGTGGGGTTGACCAGAAAT 5150 TTTCTGGTCAACCCCACAA TTGTGGGGTTGACCAGAAA 5151TTCTGGTCAACCCCACAAG CTTGTGGGGTTGACCAGAA 5152 TCTGGTCAACCCCACAAGCGCTTGTGGGGTTGACCAGA 5153 CTGGTCAACCCCACAAGCA TGCTTGTGGGGTTGACCAG 5154TGGTCAACCCCACAAGCAC GTGCTTGTGGGGTTGACCA 5155 GGTCAACCCCACAAGCACCGGTGCTTGTGGGGTTGACC 5156 GTCAACCCCACAAGCACCA TGGTGCTTGTGGGGTTGAC 5157TCAACCCCACAAGCACCAC GTGGTGCTTGTGGGGTTGA 5158 CAACCCCACAAGCACCACTAGTGGTGCTTGTGGGGTTG 5159 AACCCCACAAGCACCACTC GAGTGGTGCTTGTGGGGTT 5160ACCCCACAAGCACCACTCT AGAGTGGTGCTTGTGGGGT 5161 CCCCACAAGCACCACTCTGCAGAGTGGTGCTTGTGGGG 5162 CCCACAAGCACCACTCTGG CCAGAGTGGTGCTTGTGGG 5163CCACAAGCACCACTCTGGG CCCAGAGTGGTGCTTGTGG 5164 CACAAGCACCACTCTGGGCGCCCAGAGTGGTGCTTGTG 5165 ACAAGCACCACTCTGGGCA TGCCCAGAGTGGTGCTTGT 5166CAAGCACCACTCTGGGCAC GTGCCCAGAGTGGTGCTTG 5167 AAGCACCACTCTGGGCACATGTGCCCAGAGTGGTGCTT 5168 AGCACCACTCTGGGCACAA TTGTGCCCAGAGTGGTGCT 5169GCACCACTCTGGGCACAAG CTTGTGCCCAGAGTGGTGC 5170 CACCACTCTGGGCACAAGCGCTTGTGCCCAGAGTGGTG 5171 ACCACTCTGGGCACAAGCA TGCTTGTGCCCAGAGTGGT 5172CCACTCTGGGCACAAGCAG CTGCTTGTGCCCAGAGTGG 5173 CACTCTGGGCACAAGCAGGCCTGCTTGTGCCCAGAGTG 5174 ACTCTGGGCACAAGCAGGG CCCTGCTTGTGCCCAGAGT 5175CTCTGGGCACAAGCAGGGC GCCCTGCTTGTGCCCAGAG 5176 TCTGGGCACAAGCAGGGCATGCCCTGCTTGTGCCCAGA 5177 CTGGGCACAAGCAGGGCAC GTGCCCTGCTTGTGCCCAG 5178TGGGCACAAGCAGGGCACT AGTGCCCTGCTTGTGCCCA 5179 GGGCACAAGCAGGGCACTCGAGTGCCCTGCTTGTGCCC 5180 GGCACAAGCAGGGCACTCT AGAGTGCCCTGCTTGTGCC 5181GCACAAGCAGGGCACTCTG CAGAGTGCCCTGCTTGTGC 5182 CACAAGCAGGGCACTCTGTACAGAGTGCCCTGCTTGTG 5183 ACAAGCAGGGCACTCTGTT AACAGAGTGCCCTGCTTGT 5184CAAGCAGGGCACTCTGTTC GAACAGAGTGCCCTGCTTG 5185 AAGCAGGGCACTCTGTTCCGGAACAGAGTGCCCTGCTT 5186 AGCAGGGCACTCTGTTCCC GGGAACAGAGTGCCCTGCT 5187GCAGGGCACTCTGTTCCCC GGGGAACAGAGTGCCCTGC 5188 CAGGGCACTCTGTTCCCCTAGGGGAACAGAGTGCCCTG 5189 AGGGCACTCTGTTCCCCTC GAGGGGAACAGAGTGCCCT 5190GGGCACTCTGTTCCCCTCC GGAGGGGAACAGAGTGCCC 5191 GGCACTCTGTTCCCCTCCCGGGAGGGGAACAGAGTGCC 5192 GCACTCTGTTCCCCTCCCC GGGGAGGGGAACAGAGTGC 5193CACTCTGTTCCCCTCCCCC GGGGGAGGGGAACAGAGTG 5194 ACTCTGTTCCCCTCCCCCTAGGGGGAGGGGAACAGAGT 5195 CTCTGTTCCCCTCCCCCTT AAGGGGGAGGGGAACAGAG 5196TCTGTTCCCCTCCCCCTTA TAAGGGGGAGGGGAACAGA 5197 CTGTTCCCCTCCCCCTTAATTAAGGGGGAGGGGAACAG 5198 TGTTCCCCTCCCCCTTAAG CTTAAGGGGGAGGGGAACA 5199GTTCCCCTCCCCCTTAAGC GCTTAAGGGGGAGGGGAAC 5200 TTCCCCTCCCCCTTAAGCCGGCTTAAGGGGGAGGGGAA 5201 TCCCCTCCCCCTTAAGCCA TGGCTTAAGGGGGAGGGGA 5202CCCCTCCCCCTTAAGCCAA TTGGCTTAAGGGGGAGGGG 5203 CCCTCCCCCTTAAGCCAACGTTGGCTTAAGGGGGAGGG 5204 CCTCCCCCTTAAGCCAACA TGTTGGCTTAAGGGGGAGG 5205CTCCCCCTTAAGCCAACAA TTGTTGGCTTAAGGGGGAG 5206 TCCCCCTTAAGCCAACAACGTTGTTGGCTTAAGGGGGA 5207 CCCCCTTAAGCCAACAACC GGTTGTTGGCTTAAGGGGG 5208CCCCTTAAGCCAACAACCA TGGTTGTTGGCTTAAGGGG 5209 CCCTTAAGCCAACAACCACGTGGTTGTTGGCTTAAGGG 5210 CCTTAAGCCAACAACCACA TGTGGTTGTTGGCTTAAGG 5211CTTAAGCCAACAACCACAG CTGTGGTTGTTGGCTTAAG 5212 TTAAGCCAACAACCACAGTACTGTGGTTGTTGGCTTAA 5213 TAAGCCAACAACCACAGTG CACTGTGGTTGTTGGCTTA 5214AAGCCAACAACCACAGTGC GCACTGTGGTTGTTGGCTT 5215 AGCCAACAACCACAGTGCCGGCACTGTGGTTGTTGGCT 5216 GCCAACAACCACAGTGCCA TGGCACTGTGGTTGTTGGC 5217CCAACAACCACAGTGCCAC GTGGCACTGTGGTTGTTGG 5218 CAACAACCACAGTGCCACCGGTGGCACTGTGGTTGTTG 5219 AACAACCACAGTGCCACCA TGGTGGCACTGTGGTTGTT 5220ACAACCACAGTGCCACCAA TTGGTGGCACTGTGGTTGT 5221 CAACCACAGTGCCACCAAGCTTGGTGGCACTGTGGTTG 5222 AACCACAGTGCCACCAAGC GCTTGGTGGCACTGTGGTT 5223ACCACAGTGCCACCAAGCT AGCTTGGTGGCACTGTGGT 5224 CCACAGTGCCACCAAGCTCGAGCTTGGTGGCACTGTGG 5225 CACAGTGCCACCAAGCTCA TGAGCTTGGTGGCACTGTG 5226ACAGTGCCACCAAGCTCAC GTGAGCTTGGTGGCACTGT 5227 CAGTGCCACCAAGCTCACATGTGAGCTTGGTGGCACTG 5228 AGTGCCACCAAGCTCACAC GTGTGAGCTTGGTGGCACT 5229GTGCCACCAAGCTCACACC GGTGTGAGCTTGGTGGCAC 5230 TGCCACCAAGCTCACACCTAGGTGTGAGCTTGGTGGCA 5231 GCCACCAAGCTCACACCTG CAGGTGTGAGCTTGGTGGC 5232CCACCAAGCTCACACCTGT ACAGGTGTGAGCTTGGTGG 5233 CACCAAGCTCACACCTGTCGACAGGTGTGAGCTTGGTG 5234 ACCAAGCTCACACCTGTCC GGACAGGTGTGAGCTTGGT 5235CCAAGCTCACACCTGTCCT AGGACAGGTGTGAGCTTGG 5236 CAAGCTCACACCTGTCCTTAAGGACAGGTGTGAGCTTG 5237 AAGCTCACACCTGTCCTTC GAAGGACAGGTGTGAGCTT 5238AGCTCACACCTGTCCTTCT AGAAGGACAGGTGTGAGCT 5239 GCTCACACCTGTCCTTCTCGAGAAGGACAGGTGTGAGC 5240 CTCACACCTGTCCTTCTCA TGAGAAGGACAGGTGTGAG 5241TCACACCTGTCCTTCTCAG CTGAGAAGGACAGGTGTGA 5242 CACACCTGTCCTTCTCAGGCCTGAGAAGGACAGGTGTG 5243 ACACCTGTCCTTCTCAGGC GCCTGAGAAGGACAGGTGT 5244CACCTGTCCTTCTCAGGCT AGCCTGAGAAGGACAGGTG 5245 ACCTGTCCTTCTCAGGCTGCAGCCTGAGAAGGACAGGT 5246 CCTGTCCTTCTCAGGCTGG CCAGCCTGAGAAGGACAGG 5247CTGTCCTTCTCAGGCTGGC GCCAGCCTGAGAAGGACAG 5248 TGTCCTTCTCAGGCTGGCATGCCAGCCTGAGAAGGACA 5249 GTCCTTCTCAGGCTGGCAT ATGCCAGCCTGAGAAGGAC 5250TCCTTCTCAGGCTGGCATC GATGCCAGCCTGAGAAGGA 5251 CCTTCTCAGGCTGGCATCTAGATGCCAGCCTGAGAAGG 5252 CTTCTCAGGCTGGCATCTC GAGATGCCAGCCTGAGAAG 5253TTCTCAGGCTGGCATCTCC GGAGATGCCAGCCTGAGAA 5254 TCTCAGGCTGGCATCTCCCGGGAGATGCCAGCCTGAGA 5255 CTCAGGCTGGCATCTCCCC GGGGAGATGCCAGCCTGAG 5256TCAGGCTGGCATCTCCCCC GGGGGAGATGCCAGCCTGA 5257 CAGGCTGGCATCTCCCCCATGGGGGAGATGCCAGCCTG 5258 AGGCTGGCATCTCCCCCAC GTGGGGGAGATGCCAGCCT 5259GGCTGGCATCTCCCCCACC GGTGGGGGAGATGCCAGCC 5260 GCTGGCATCTCCCCCACCCGGGTGGGGGAGATGCCAGC 5261 CTGGCATCTCCCCCACCCT AGGGTGGGGGAGATGCCAG 5262TGGCATCTCCCCCACCCTG CAGGGTGGGGGAGATGCCA 5263 GGCATCTCCCCCACCCTGTACAGGGTGGGGGAGATGCC 5264 GCATCTCCCCCACCCTGTG CACAGGGTGGGGGAGATGC 5265CATCTCCCCCACCCTGTGC GCACAGGGTGGGGGAGATG 5266 ATCTCCCCCACCCTGTGCCGGCACAGGGTGGGGGAGAT 5267 TCTCCCCCACCCTGTGCCC GGGCACAGGGTGGGGGAGA 5268CTCCCCCACCCTGTGCCCC GGGGCACAGGGTGGGGGAG 5269 TCCCCCACCCTGTGCCCCTAGGGGCACAGGGTGGGGGA 5270 CCCCCACCCTGTGCCCCTT AAGGGGCACAGGGTGGGGG 5271CCCCACCCTGTGCCCCTTT AAAGGGGCACAGGGTGGGG 5272 CCCACCCTGTGCCCCTTTTAAAAGGGGCACAGGGTGGG 5273 CCACCCTGTGCCCCTTTTC GAAAAGGGGCACAGGGTGG 5274CACCCTGTGCCCCTTTTCA TGAAAAGGGGCACAGGGTG 5275 ACCCTGTGCCCCTTTTCATATGAAAAGGGGCACAGGGT 5276 CCCTGTGCCCCTTTTCATG CATGAAAAGGGGCACAGGG 5277CCTGTGCCCCTTTTCATGG CCATGAAAAGGGGCACAGG 5278 CTGTGCCCCTTTTCATGGTACCATGAAAAGGGGCACAG 5279 TGTGCCCCTTTTCATGGTA TACCATGAAAAGGGGCACA 5280GTGCCCCTTTTCATGGTAC GTACCATGAAAAGGGGCAC 5281 TGCCCCTTTTCATGGTACCGGTACCATGAAAAGGGGCA 5282 GCCCCTTTTCATGGTACCA TGGTACCATGAAAAGGGGC 5283CCCCTTTTCATGGTACCAG CTGGTACCATGAAAAGGGG 5284 CCCTTTTCATGGTACCAGGCCTGGTACCATGAAAAGGG 5285 CCTTTTCATGGTACCAGGC GCCTGGTACCATGAAAAGG 5286CTTTTCATGGTACCAGGCC GGCCTGGTACCATGAAAAG 5287 TTTTCATGGTACCAGGCCCGGGCCTGGTACCATGAAAA 5288 TTTCATGGTACCAGGCCCG CGGGCCTGGTACCATGAAA 5289TTCATGGTACCAGGCCCGC GCGGGCCTGGTACCATGAA 5290 TCATGGTACCAGGCCCGCATGCGGGCCTGGTACCATGA 5291 CATGGTACCAGGCCCGCAC GTGCGGGCCTGGTACCATG 5292ATGGTACCAGGCCCGCACT AGTGCGGGCCTGGTACCAT 5293 TGGTACCAGGCCCGCACTGCAGTGCGGGCCTGGTACCA 5294 GGTACCAGGCCCGCACTGG CCAGTGCGGGCCTGGTACC 5295GTACCAGGCCCGCACTGGG CCCAGTGCGGGCCTGGTAC 5296 TACCAGGCCCGCACTGGGGCCCCAGTGCGGGCCTGGTA 5297 ACCAGGCCCGCACTGGGGG CCCCCAGTGCGGGCCTGGT 5298CCAGGCCCGCACTGGGGGC GCCCCCAGTGCGGGCCTGG 5299 CAGGCCCGCACTGGGGGCATGCCCCCAGTGCGGGCCTG 5300 AGGCCCGCACTGGGGGCAA TTGCCCCCAGTGCGGGCCT 5301GGCCCGCACTGGGGGCAAT ATTGCCCCCAGTGCGGGCC 5302 GCCCGCACTGGGGGCAATTAATTGCCCCCAGTGCGGGC 5303 CCCGCACTGGGGGCAATTG CAATTGCCCCCAGTGCGGG 5304CCGCACTGGGGGCAATTGA TCAATTGCCCCCAGTGCGG 5305 CGCACTGGGGGCAATTGACGTCAATTGCCCCCAGTGCG 5306 GCACTGGGGGCAATTGACT AGTCAATTGCCCCCAGTGC 5307CACTGGGGGCAATTGACTT AAGTCAATTGCCCCCAGTG 5308 ACTGGGGGCAATTGACTTCGAAGTCAATTGCCCCCAGT 5309 CTGGGGGCAATTGACTTCC GGAAGTCAATTGCCCCCAG 5310TGGGGGCAATTGACTTCCT AGGAAGTCAATTGCCCCCA 5311 GGGGGCAATTGACTTCCTCGAGGAAGTCAATTGCCCCC 5312 GGGGCAATTGACTTCCTCC GGAGGAAGTCAATTGCCCC 5313GGGCAATTGACTTCCTCCA TGGAGGAAGTCAATTGCCC 5314 GGCAATTGACTTCCTCCAATTGGAGGAAGTCAATTGCC 5315 GCAATTGACTTCCTCCAAT ATTGGAGGAAGTCAATTGC 5316CAATTGACTTCCTCCAATC GATTGGAGGAAGTCAATTG 5317 AATTGACTTCCTCCAATCCGGATTGGAGGAAGTCAATT 5318 ATTGACTTCCTCCAATCCC GGGATTGGAGGAAGTCAAT 5319TTGACTTCCTCCAATCCCC GGGGATTGGAGGAAGTCAA 5320 TGACTTCCTCCAATCCCCATGGGGATTGGAGGAAGTCA 5321 GACTTCCTCCAATCCCCAC GTGGGGATTGGAGGAAGTC 5322ACTTCCTCCAATCCCCACT AGTGGGGATTGGAGGAAGT 5323 CTTCCTCCAATCCCCACTCGAGTGGGGATTGGAGGAAG 5324 TTCCTCCAATCCCCACTCC GGAGTGGGGATTGGAGGAA 5325TCCTCCAATCCCCACTCCT AGGAGTGGGGATTGGAGGA 5326 CCTCCAATCCCCACTCCTCGAGGAGTGGGGATTGGAGG 5327 CTCCAATCCCCACTCCTCC GGAGGAGTGGGGATTGGAG 5328TCCAATCCCCACTCCTCCG CGGAGGAGTGGGGATTGGA 5329 CCAATCCCCACTCCTCCGATCGGAGGAGTGGGGATTGG 5330 CAATCCCCACTCCTCCGAG CTCGGAGGAGTGGGGATTG 5331AATCCCCACTCCTCCGAGA TCTCGGAGGAGTGGGGATT 5332 ATCCCCACTCCTCCGAGACGTCTCGGAGGAGTGGGGAT 5333 TCCCCACTCCTCCGAGACC GGTCTCGGAGGAGTGGGGA 5334CCCCACTCCTCCGAGACCC GGGTCTCGGAGGAGTGGGG 5335 CCCACTCCTCCGAGACCCATGGGTCTCGGAGGAGTGGG 5336 CCACTCCTCCGAGACCCAG CTGGGTCTCGGAGGAGTGG 5337CACTCCTCCGAGACCCAGG CCTGGGTCTCGGAGGAGTG 5338 ACTCCTCCGAGACCCAGGATCCTGGGTCTCGGAGGAGT 5339 CTCCTCCGAGACCCAGGAG CTCCTGGGTCTCGGAGGAG 5340TCCTCCGAGACCCAGGAGA TCTCCTGGGTCTCGGAGGA 5341 CCTCCGAGACCCAGGAGACGTCTCCTGGGTCTCGGAGG 5342 CTCCGAGACCCAGGAGACA TGTCTCCTGGGTCTCGGAG 5343TCCGAGACCCAGGAGACAA TTGTCTCCTGGGTCTCGGA 5344 CCGAGACCCAGGAGACAAATTTGTCTCCTGGGTCTCGG 5345 CGAGACCCAGGAGACAAAC GTTTGTCTCCTGGGTCTCG 5346GAGACCCAGGAGACAAACA TGTTTGTCTCCTGGGTCTC 5347 AGACCCAGGAGACAAACAGCTGTTTGTCTCCTGGGTCT 5348 GACCCAGGAGACAAACAGC GCTGTTTGTCTCCTGGGTC 5349ACCCAGGAGACAAACAGCC GGCTGTTTGTCTCCTGGGT 5350 CCCAGGAGACAAACAGCCCGGGCTGTTTGTCTCCTGGG 5351 CCAGGAGACAAACAGCCCT AGGGCTGTTTGTCTCCTGG 5352CAGGAGACAAACAGCCCTT AAGGGCTGTTTGTCTCCTG 5353 AGGAGACAAACAGCCCTTCGAAGGGCTGTTTGTCTCCT 5354 GGAGACAAACAGCCCTTCC GGAAGGGCTGTTTGTCTCC 5355GAGACAAACAGCCCTTCCT AGGAAGGGCTGTTTGTCTC 5356 AGACAAACAGCCCTTCCTTAAGGAAGGGCTGTTTGTCT 5357 GACAAACAGCCCTTCCTTG CAAGGAAGGGCTGTTTGTC 5358ACAAACAGCCCTTCCTTGG CCAAGGAAGGGCTGTTTGT 5359 CAAACAGCCCTTCCTTGGGCCCAAGGAAGGGCTGTTTG 5360 AAACAGCCCTTCCTTGGGG CCCCAAGGAAGGGCTGTTT 5361AACAGCCCTTCCTTGGGGA TCCCCAAGGAAGGGCTGTT 5362 ACAGCCCTTCCTTGGGGAATTCCCCAAGGAAGGGCTGT 5363 CAGCCCTTCCTTGGGGAAA TTTCCCCAAGGAAGGGCTG 5364AGCCCTTCCTTGGGGAAAC GTTTCCCCAAGGAAGGGCT 5365 GCCCTTCCTTGGGGAAACTAGTTTCCCCAAGGAAGGGC 5366 CCCTTCCTTGGGGAAACTT AAGTTTCCCCAAGGAAGGG 5367CCTTCCTTGGGGAAACTTG CAAGTTTCCCCAAGGAAGG 5368 CTTCCTTGGGGAAACTTGGCCAAGTTTCCCCAAGGAAG 5369 TTCCTTGGGGAAACTTGGG CCCAAGTTTCCCCAAGGAA 5370TCCTTGGGGAAACTTGGGA TCCCAAGTTTCCCCAAGGA 5371 CCTTGGGGAAACTTGGGAATTCCCAAGTTTCCCCAAGG 5372 CTTGGGGAAACTTGGGAAT ATTCCCAAGTTTCCCCAAG 5373TTGGGGAAACTTGGGAATC GATTCCCAAGTTTCCCCAA 5374 TGGGGAAACTTGGGAATCATGATTCCCAAGTTTCCCCA 5375 GGGGAAACTTGGGAATCAT ATGATTCCCAAGTTTCCCC 5376GGGAAACTTGGGAATCATT AATGATTCCCAAGTTTCCC 5377 GGAAACTTGGGAATCATTCGAATGATTCCCAAGTTTCC 5378 GAAACTTGGGAATCATTCT AGAATGATTCCCAAGTTTC 5379AAACTTGGGAATCATTCTG CAGAATGATTCCCAAGTTT 5380 AACTTGGGAATCATTCTGGCCAGAATGATTCCCAAGTT 5381 ACTTGGGAATCATTCTGGC GCCAGAATGATTCCCAAGT 5382CTTGGGAATCATTCTGGCT AGCCAGAATGATTCCCAAG 5383 TTGGGAATCATTCTGGCTTAAGCCAGAATGATTCCCAA 5384 TGGGAATCATTCTGGCTTA TAAGCCAGAATGATTCCCA 5385GGGAATCATTCTGGCTTAA TTAAGCCAGAATGATTCCC 5386 GGAATCATTCTGGCTTAAATTTAAGCCAGAATGATTCC 5387 GAATCATTCTGGCTTAAAC GTTTAAGCCAGAATGATTC 5388AATCATTCTGGCTTAAACA TGTTTAAGCCAGAATGATT 5389 ATCATTCTGGCTTAAACAATTGTTTAAGCCAGAATGAT 5390 TCATTCTGGCTTAAACAAC GTTGTTTAAGCCAGAATGA 5391CATTCTGGCTTAAACAACA TGTTGTTTAAGCCAGAATG 5392 ATTCTGGCTTAAACAACACGTGTTGTTTAAGCCAGAAT 5393 TTCTGGCTTAAACAACACC GGTGTTGTTTAAGCCAGAA 5394TCTGGCTTAAACAACACCT AGGTGTTGTTTAAGCCAGA 5395 CTGGCTTAAACAACACCTCGAGGTGTTGTTTAAGCCAG 5396 TGGCTTAAACAACACCTCC GGAGGTGTTGTTTAAGCCA 5397GGCTTAAACAACACCTCCT AGGAGGTGTTGTTTAAGCC 5398 GCTTAAACAACACCTCCTCGAGGAGGTGTTGTTTAAGC 5399 CTTAAACAACACCTCCTCC GGAGGAGGTGTTGTTTAAG 5400TTAAACAACACCTCCTCCT AGGAGGAGGTGTTGTTTAA 5401 TAAACAACACCTCCTCCTGCAGGAGGAGGTGTTGTTTA 5402 AAACAACACCTCCTCCTGC GCAGGAGGAGGTGTTGTTT 5403AACAACACCTCCTCCTGCT AGCAGGAGGAGGTGTTGTT 5404 ACAACACCTCCTCCTGCTGCAGCAGGAGGAGGTGTTGT 5405 CAACACCTCCTCCTGCTGC GCAGCAGGAGGAGGTGTTG 5406AACACCTCCTCCTGCTGCT AGCAGCAGGAGGAGGTGTT 5407 ACACCTCCTCCTGCTGCTCGAGCAGCAGGAGGAGGTGT 5408 CACCTCCTCCTGCTGCTCA TGAGCAGCAGGAGGAGGTG 5409ACCTCCTCCTGCTGCTCAC GTGAGCAGCAGGAGGAGGT 5410 CCTCCTCCTGCTGCTCACTAGTGAGCAGCAGGAGGAGG 5411 CTCCTCCTGCTGCTCACTC GAGTGAGCAGCAGGAGGAG 5412TCCTCCTGCTGCTCACTCC GGAGTGAGCAGCAGGAGGA 5413 CCTCCTGCTGCTCACTCCCGGGAGTGAGCAGCAGGAGG 5414 CTCCTGCTGCTCACTCCCG CGGGAGTGAGCAGCAGGAG 5415TCCTGCTGCTCACTCCCGC GCGGGAGTGAGCAGCAGGA 5416 CCTGCTGCTCACTCCCGCTAGCGGGAGTGAGCAGCAGG 5417 CTGCTGCTCACTCCCGCTG CAGCGGGAGTGAGCAGCAG 5418TGCTGCTCACTCCCGCTGA TCAGCGGGAGTGAGCAGCA 5419 GCTGCTCACTCCCGCTGAGCTCAGCGGGAGTGAGCAGC 5420 CTGCTCACTCCCGCTGAGC GCTCAGCGGGAGTGAGCAG 5421TGCTCACTCCCGCTGAGCC GGCTCAGCGGGAGTGAGCA 5422 GCTCACTCCCGCTGAGCCCGGGCTCAGCGGGAGTGAGC 5423 CTCACTCCCGCTGAGCCCA TGGGCTCAGCGGGAGTGAG 5424TCACTCCCGCTGAGCCCAC GTGGGCTCAGCGGGAGTGA 5425 CACTCCCGCTGAGCCCACTAGTGGGCTCAGCGGGAGTG 5426 ACTCCCGCTGAGCCCACTC GAGTGGGCTCAGCGGGAGT 5427CTCCCGCTGAGCCCACTCT AGAGTGGGCTCAGCGGGAG 5428 TCCCGCTGAGCCCACTCTATAGAGTGGGCTCAGCGGGA 5429 CCCGCTGAGCCCACTCTAC GTAGAGTGGGCTCAGCGGG 5430CCGCTGAGCCCACTCTACT AGTAGAGTGGGCTCAGCGG 5431 CGCTGAGCCCACTCTACTGCAGTAGAGTGGGCTCAGCG 5432 GCTGAGCCCACTCTACTGC GCAGTAGAGTGGGCTCAGC 5433CTGAGCCCACTCTACTGCC GGCAGTAGAGTGGGCTCAG 5434 TGAGCCCACTCTACTGCCCGGGCAGTAGAGTGGGCTCA 5435 GAGCCCACTCTACTGCCCC GGGGCAGTAGAGTGGGCTC 5436AGCCCACTCTACTGCCCCA TGGGGCAGTAGAGTGGGCT 5437 GCCCACTCTACTGCCCCAGCTGGGGCAGTAGAGTGGGC 5438 CCCACTCTACTGCCCCAGC GCTGGGGCAGTAGAGTGGG 5439CCACTCTACTGCCCCAGCT AGCTGGGGCAGTAGAGTGG 5440 CACTCTACTGCCCCAGCTCGAGCTGGGGCAGTAGAGTG 5441 ACTCTACTGCCCCAGCTCC GGAGCTGGGGCAGTAGAGT 5442CTCTACTGCCCCAGCTCCG CGGAGCTGGGGCAGTAGAG 5443 TCTACTGCCCCAGCTCCGTACGGAGCTGGGGCAGTAGA 5444 CTACTGCCCCAGCTCCGTT AACGGAGCTGGGGCAGTAG 5445TACTGCCCCAGCTCCGTTT AAACGGAGCTGGGGCAGTA 5446 ACTGCCCCAGCTCCGTTTCGAAACGGAGCTGGGGCAGT 5447 CTGCCCCAGCTCCGTTTCT AGAAACGGAGCTGGGGCAG 5448TGCCCCAGCTCCGTTTCTA TAGAAACGGAGCTGGGGCA 5449 GCCCCAGCTCCGTTTCTACGTAGAAACGGAGCTGGGGC 5450 CCCCAGCTCCGTTTCTACC GGTAGAAACGGAGCTGGGG 5451CCCAGCTCCGTTTCTACCA TGGTAGAAACGGAGCTGGG 5452 CCAGCTCCGTTTCTACCACGTGGTAGAAACGGAGCTGG 5453 CAGCTCCGTTTCTACCACC GGTGGTAGAAACGGAGCTG 5454AGCTCCGTTTCTACCACCG CGGTGGTAGAAACGGAGCT 5455 GCTCCGTTTCTACCACCGCGCGGTGGTAGAAACGGAGC 5456 CTCCGTTTCTACCACCGCA TGCGGTGGTAGAAACGGAG 5457TCCGTTTCTACCACCGCAT ATGCGGTGGTAGAAACGGA 5458 CCGTTTCTACCACCGCATCGATGCGGTGGTAGAAACGG 5459 CGTTTCTACCACCGCATCC GGATGCGGTGGTAGAAACG 5460GTTTCTACCACCGCATCCT AGGATGCGGTGGTAGAAAC 5461 TTTCTACCACCGCATCCTCGAGGATGCGGTGGTAGAAA 5462 TTCTACCACCGCATCCTCA TGAGGATGCGGTGGTAGAA 5463TCTACCACCGCATCCTCAC GTGAGGATGCGGTGGTAGA 5464 CTACCACCGCATCCTCACTAGTGAGGATGCGGTGGTAG 5465 TACCACCGCATCCTCACTG CAGTGAGGATGCGGTGGTA 5466ACCACCGCATCCTCACTGG CCAGTGAGGATGCGGTGGT 5467 CCACCGCATCCTCACTGGGCCCAGTGAGGATGCGGTGG 5468 CACCGCATCCTCACTGGGC GCCCAGTGAGGATGCGGTG 5469ACCGCATCCTCACTGGGCT AGCCCAGTGAGGATGCGGT 5470 CCGCATCCTCACTGGGCTCGAGCCCAGTGAGGATGCGG 5471 CGCATCCTCACTGGGCTCA TGAGCCCAGTGAGGATGCG 5472GCATCCTCACTGGGCTCAC GTGAGCCCAGTGAGGATGC 5473 CATCCTCACTGGGCTCACTAGTGAGCCCAGTGAGGATG 5474 ATCCTCACTGGGCTCACTG CAGTGAGCCCAGTGAGGAT 5475TCCTCACTGGGCTCACTGC GCAGTGAGCCCAGTGAGGA 5476 CCTCACTGGGCTCACTGCATGCAGTGAGCCCAGTGAGG 5477 CTCACTGGGCTCACTGCAG CTGCAGTGAGCCCAGTGAG 5478TCACTGGGCTCACTGCAGG CCTGCAGTGAGCCCAGTGA 5479 CACTGGGCTCACTGCAGGCGCCTGCAGTGAGCCCAGTG 5480 ACTGGGCTCACTGCAGGCA TGCCTGCAGTGAGCCCAGT 5481CTGGGCTCACTGCAGGCAT ATGCCTGCAGTGAGCCCAG 5482 TGGGCTCACTGCAGGCATGCATGCCTGCAGTGAGCCCA 5483 GGGCTCACTGCAGGCATGC GCATGCCTGCAGTGAGCCC 5484GGCTCACTGCAGGCATGCT AGCATGCCTGCAGTGAGCC 5485 GCTCACTGCAGGCATGCTGCAGCATGCCTGCAGTGAGC 5486 CTCACTGCAGGCATGCTGA TCAGCATGCCTGCAGTGAG 5487TCACTGCAGGCATGCTGAA TTCAGCATGCCTGCAGTGA 5488 CACTGCAGGCATGCTGAACGTTCAGCATGCCTGCAGTG 5489 ACTGCAGGCATGCTGAACA TGTTCAGCATGCCTGCAGT 5490CTGCAGGCATGCTGAACAA TTGTTCAGCATGCCTGCAG 5491 TGCAGGCATGCTGAACAAGCTTGTTCAGCATGCCTGCA 5492 GCAGGCATGCTGAACAAGG CCTTGTTCAGCATGCCTGC 5493CAGGCATGCTGAACAAGGG CCCTTGTTCAGCATGCCTG 5494 AGGCATGCTGAACAAGGGGCCCCTTGTTCAGCATGCCT 5495 GGCATGCTGAACAAGGGGC GCCCCTTGTTCAGCATGCC 5496GCATGCTGAACAAGGGGCC GGCCCCTTGTTCAGCATGC 5497 CATGCTGAACAAGGGGCCTAGGCCCCTTGTTCAGCATG 5498 ATGCTGAACAAGGGGCCTC GAGGCCCCTTGTTCAGCAT 5499TGCTGAACAAGGGGCCTCC GGAGGCCCCTTGTTCAGCA 5500 GCTGAACAAGGGGCCTCCATGGAGGCCCCTTGTTCAGC 5501 CTGAACAAGGGGCCTCCAA TTGGAGGCCCCTTGTTCAG 5502TGAACAAGGGGCCTCCAAC GTTGGAGGCCCCTTGTTCA 5503 GAACAAGGGGCCTCCAACCGGTTGGAGGCCCCTTGTTC 5504 AACAAGGGGCCTCCAACCT AGGTTGGAGGCCCCTTGTT 5505ACAAGGGGCCTCCAACCTT AAGGTTGGAGGCCCCTTGT 5506 CAAGGGGCCTCCAACCTTCGAAGGTTGGAGGCCCCTTG 5507 AAGGGGCCTCCAACCTTCT AGAAGGTTGGAGGCCCCTT 5508AGGGGCCTCCAACCTTCTG CAGAAGGTTGGAGGCCCCT 5509 GGGGCCTCCAACCTTCTGCGCAGAAGGTTGGAGGCCCC 5510 GGGCCTCCAACCTTCTGCC GGCAGAAGGTTGGAGGCCC 5511GGCCTCCAACCTTCTGCCC GGGCAGAAGGTTGGAGGCC 5512 GCCTCCAACCTTCTGCCCTAGGGCAGAAGGTTGGAGGC 5513 CCTCCAACCTTCTGCCCTC GAGGGCAGAAGGTTGGAGG 5514CTCCAACCTTCTGCCCTCC GGAGGGCAGAAGGTTGGAG 5515 TCCAACCTTCTGCCCTCCTAGGAGGGCAGAAGGTTGGA 5516 CCAACCTTCTGCCCTCCTG CAGGAGGGCAGAAGGTTGG 5517CAACCTTCTGCCCTCCTGC GCAGGAGGGCAGAAGGTTG 5518 AACCTTCTGCCCTCCTGCCGGCAGGAGGGCAGAAGGTT 5519 ACCTTCTGCCCTCCTGCCA TGGCAGGAGGGCAGAAGGT 5520CCTTCTGCCCTCCTGCCAA TTGGCAGGAGGGCAGAAGG 5521 CTTCTGCCCTCCTGCCAAATTTGGCAGGAGGGCAGAAG 5522 TTCTGCCCTCCTGCCAAAA TTTTGGCAGGAGGGCAGAA 5523TCTGCCCTCCTGCCAAAAG CTTTTGGCAGGAGGGCAGA 5524 CTGCCCTCCTGCCAAAAGATCTTTTGGCAGGAGGGCAG 5525 TGCCCTCCTGCCAAAAGAT ATCTTTTGGCAGGAGGGCA 5526GCCCTCCTGCCAAAAGATC GATCTTTTGGCAGGAGGGC 5527 CCCTCCTGCCAAAAGATCTAGATCTTTTGGCAGGAGGG 5528 CCTCCTGCCAAAAGATCTG CAGATCTTTTGGCAGGAGG 5529CTCCTGCCAAAAGATCTGG CCAGATCTTTTGGCAGGAG 5530 TCCTGCCAAAAGATCTGGGCCCAGATCTTTTGGCAGGA 5531 CCTGCCAAAAGATCTGGGG CCCCAGATCTTTTGGCAGG 5532CTGCCAAAAGATCTGGGGA TCCCCAGATCTTTTGGCAG 5533 TGCCAAAAGATCTGGGGAGCTCCCCAGATCTTTTGGCA 5534 GCCAAAAGATCTGGGGAGT ACTCCCCAGATCTTTTGGC 5535CCAAAAGATCTGGGGAGTG CACTCCCCAGATCTTTTGG 5536 CAAAAGATCTGGGGAGTGTACACTCCCCAGATCTTTTG 5537 AAAAGATCTGGGGAGTGTG CACACTCCCCAGATCTTTT 5538AAAGATCTGGGGAGTGTGA TCACACTCCCCAGATCTTT 5539 AAGATCTGGGGAGTGTGAGCTCACACTCCCCAGATCTT 5540 AGATCTGGGGAGTGTGAGG CCTCACACTCCCCAGATCT 5541GATCTGGGGAGTGTGAGGA TCCTCACACTCCCCAGATC 5542 ATCTGGGGAGTGTGAGGAGCTCCTCACACTCCCCAGAT 5543 TCTGGGGAGTGTGAGGAGA TCTCCTCACACTCCCCAGA 5544CTGGGGAGTGTGAGGAGAG CTCTCCTCACACTCCCCAG 5545 TGGGGAGTGTGAGGAGAGGCCTCTCCTCACACTCCCCA 5546 GGGGAGTGTGAGGAGAGGG CCCTCTCCTCACACTCCCC 5547GGGAGTGTGAGGAGAGGGT ACCCTCTCCTCACACTCCC 5548 GGAGTGTGAGGAGAGGGTGCACCCTCTCCTCACACTCC 5549 GAGTGTGAGGAGAGGGTGG CCACCCTCTCCTCACACTC 5550AGTGTGAGGAGAGGGTGGC GCCACCCTCTCCTCACACT 5551 GTGTGAGGAGAGGGTGGCATGCCACCCTCTCCTCACAC 5552 TGTGAGGAGAGGGTGGCAT ATGCCACCCTCTCCTCACA 5553GTGAGGAGAGGGTGGCATC GATGCCACCCTCTCCTCAC 5554 TGAGGAGAGGGTGGCATCATGATGCCACCCTCTCCTCA 5555 GAGGAGAGGGTGGCATCAG CTGATGCCACCCTCTCCTC 5556AGGAGAGGGTGGCATCAGG CCTGATGCCACCCTCTCCT 5557 GGAGAGGGTGGCATCAGGATCCTGATGCCACCCTCTCC 5558 GAGAGGGTGGCATCAGGAG CTCCTGATGCCACCCTCTC 5559AGAGGGTGGCATCAGGAGC GCTCCTGATGCCACCCTCT 5560 GAGGGTGGCATCAGGAGCTAGCTCCTGATGCCACCCTC 5561 AGGGTGGCATCAGGAGCTG CAGCTCCTGATGCCACCCT 5562GGGTGGCATCAGGAGCTGC GCAGCTCCTGATGCCACCC 5563 GGTGGCATCAGGAGCTGCTAGCAGCTCCTGATGCCACC 5564 GTGGCATCAGGAGCTGCTC GAGCAGCTCCTGATGCCAC 5565TGGCATCAGGAGCTGCTCA TGAGCAGCTCCTGATGCCA 5566 GGCATCAGGAGCTGCTCAGCTGAGCAGCTCCTGATGCC 5567 GCATCAGGAGCTGCTCAGG CCTGAGCAGCTCCTGATGC 5568CATCAGGAGCTGCTCAGGC GCCTGAGCAGCTCCTGATG 5569 ATCAGGAGCTGCTCAGGCTAGCCTGAGCAGCTCCTGAT 5570 TCAGGAGCTGCTCAGGCTT AAGCCTGAGCAGCTCCTGA 5571CAGGAGCTGCTCAGGCTTG CAAGCCTGAGCAGCTCCTG 5572 AGGAGCTGCTCAGGCTTGGCCAAGCCTGAGCAGCTCCT 5573 GGAGCTGCTCAGGCTTGGC GCCAAGCCTGAGCAGCTCC 5574GAGCTGCTCAGGCTTGGCG CGCCAAGCCTGAGCAGCTC 5575 AGCTGCTCAGGCTTGGCGGCCGCCAAGCCTGAGCAGCT 5576 GCTGCTCAGGCTTGGCGGA TCCGCCAAGCCTGAGCAGC 5577CTGCTCAGGCTTGGCGGAG CTCCGCCAAGCCTGAGCAG 5578 TGCTCAGGCTTGGCGGAGGCCTCCGCCAAGCCTGAGCA 5579 GCTCAGGCTTGGCGGAGGG CCCTCCGCCAAGCCTGAGC 5580CTCAGGCTTGGCGGAGGGA TCCCTCCGCCAAGCCTGAG 5581 TCAGGCTTGGCGGAGGGAGCTCCCTCCGCCAAGCCTGA 5582 CAGGCTTGGCGGAGGGAGC GCTCCCTCCGCCAAGCCTG 5583AGGCTTGGCGGAGGGAGCG CGCTCCCTCCGCCAAGCCT 5584 GGCTTGGCGGAGGGAGCGGCCGCTCCCTCCGCCAAGCC 5585 GCTTGGCGGAGGGAGCGGC GCCGCTCCCTCCGCCAAGC 5586CTTGGCGGAGGGAGCGGCA TGCCGCTCCCTCCGCCAAG 5587 TTGGCGGAGGGAGCGGCATATGCCGCTCCCTCCGCCAA 5588 TGGCGGAGGGAGCGGCATG CATGCCGCTCCCTCCGCCA 5589GGCGGAGGGAGCGGCATGG CCATGCCGCTCCCTCCGCC 5590 GCGGAGGGAGCGGCATGGGCCCATGCCGCTCCCTCCGC 5591 CGGAGGGAGCGGCATGGGC GCCCATGCCGCTCCCTCCG 5592GGAGGGAGCGGCATGGGCG CGCCCATGCCGCTCCCTCC 5593 GAGGGAGCGGCATGGGCGATCGCCCATGCCGCTCCCTC 5594 AGGGAGCGGCATGGGCGAT ATCGCCCATGCCGCTCCCT 5595GGGAGCGGCATGGGCGATG CATCGCCCATGCCGCTCCC 5596 GGAGCGGCATGGGCGATGTACATCGCCCATGCCGCTCC 5597 GAGCGGCATGGGCGATGTC GACATCGCCCATGCCGCTC 5598AGCGGCATGGGCGATGTCA TGACATCGCCCATGCCGCT 5599 GCGGCATGGGCGATGTCACGTGACATCGCCCATGCCGC 5600 CGGCATGGGCGATGTCACT AGTGACATCGCCCATGCCG 5601GGCATGGGCGATGTCACTC GAGTGACATCGCCCATGCC 5602 GCATGGGCGATGTCACTCATGAGTGACATCGCCCATGC 5603 CATGGGCGATGTCACTCAG CTGAGTGACATCGCCCATG 5604ATGGGCGATGTCACTCAGC GCTGAGTGACATCGCCCAT 5605 TGGGCGATGTCACTCAGCCGGCTGAGTGACATCGCCCA 5606 GGGCGATGTCACTCAGCCC GGGCTGAGTGACATCGCCC 5607GGCGATGTCACTCAGCCCC GGGGCTGAGTGACATCGCC 5608 GCGATGTCACTCAGCCCCTAGGGGCTGAGTGACATCGC 5609 CGATGTCACTCAGCCCCTT AAGGGGCTGAGTGACATCG 5610GATGTCACTCAGCCCCTTC GAAGGGGCTGAGTGACATC 5611 ATGTCACTCAGCCCCTTCCGGAAGGGGCTGAGTGACAT 5612 TGTCACTCAGCCCCTTCCC GGGAAGGGGCTGAGTGACA 5613GTCACTCAGCCCCTTCCCG CGGGAAGGGGCTGAGTGAC 5614 TCACTCAGCCCCTTCCCGGCCGGGAAGGGGCTGAGTGA 5615 CACTCAGCCCCTTCCCGGT ACCGGGAAGGGGCTGAGTG 5616ACTCAGCCCCTTCCCGGTC GACCGGGAAGGGGCTGAGT 5617 CTCAGCCCCTTCCCGGTCCGGACCGGGAAGGGGCTGAG 5618 TCAGCCCCTTCCCGGTCCG CGGACCGGGAAGGGGCTGA 5619CAGCCCCTTCCCGGTCCGC GCGGACCGGGAAGGGGCTG 5620 AGCCCCTTCCCGGTCCGCCGGCGGACCGGGAAGGGGCT 5621 GCCCCTTCCCGGTCCGCCC GGGCGGACCGGGAAGGGGC 5622CCCCTTCCCGGTCCGCCCG CGGGCGGACCGGGAAGGGG 5623 CCCTTCCCGGTCCGCCCGCGCGGGCGGACCGGGAAGGG 5624 CCTTCCCGGTCCGCCCGCT AGCGGGCGGACCGGGAAGG 5625CTTCCCGGTCCGCCCGCTT AAGCGGGCGGACCGGGAAG 5626 TTCCCGGTCCGCCCGCTTCGAAGCGGGCGGACCGGGAA 5627 TCCCGGTCCGCCCGCTTCC GGAAGCGGGCGGACCGGGA 5628CCCGGTCCGCCCGCTTCCC GGGAAGCGGGCGGACCGGG 5629 CCGGTCCGCCCGCTTCCCTAGGGAAGCGGGCGGACCGG 5630 CGGTCCGCCCGCTTCCCTC GAGGGAAGCGGGCGGACCG 5631GGTCCGCCCGCTTCCCTCC GGAGGGAAGCGGGCGGACC 5632 GTCCGCCCGCTTCCCTCCTAGGAGGGAAGCGGGCGGAC 5633 TCCGCCCGCTTCCCTCCTT AAGGAGGGAAGCGGGCGGA 5634CCGCCCGCTTCCCTCCTTC GAAGGAGGGAAGCGGGCGG 5635 CGCCCGCTTCCCTCCTTCATGAAGGAGGGAAGCGGGCG 5636 GCCCGCTTCCCTCCTTCAT ATGAAGGAGGGAAGCGGGC 5637CCCGCTTCCCTCCTTCATG CATGAAGGAGGGAAGCGGG 5638 CCGCTTCCCTCCTTCATGATCATGAAGGAGGGAAGCGG 5639 CGCTTCCCTCCTTCATGAT ATCATGAAGGAGGGAAGCG 5640GCTTCCCTCCTTCATGATT AATCATGAAGGAGGGAAGC 5641 CTTCCCTCCTTCATGATTTAAATCATGAAGGAGGGAAG 5642 TTCCCTCCTTCATGATTTC GAAATCATGAAGGAGGGAA 5643TCCCTCCTTCATGATTTCC GGAAATCATGAAGGAGGGA 5644 CCCTCCTTCATGATTTCCATGGAAATCATGAAGGAGGG 5645 CCTCCTTCATGATTTCCAT ATGGAAATCATGAAGGAGG 5646CTCCTTCATGATTTCCATT AATGGAAATCATGAAGGAG 5647 TCCTTCATGATTTCCATTATAATGGAAATCATGAAGGA 5648 CCTTCATGATTTCCATTAA TTAATGGAAATCATGAAGG 5649CTTCATGATTTCCATTAAA TTTAATGGAAATCATGAAG 5650 TTCATGATTTCCATTAAAGCTTTAATGGAAATCATGAA 5651 TCATGATTTCCATTAAAGT ACTTTAATGGAAATCATGA 5652CATGATTTCCATTAAAGTC GACTTTAATGGAAATCATG 5653 ATGATTTCCATTAAAGTCTAGACTTTAATGGAAATCAT 5654 TGATTTCCATTAAAGTCTG CAGACTTTAATGGAAATCA 5655GATTTCCATTAAAGTCTGT ACAGACTTTAATGGAAATC 5656 ATTTCCATTAAAGTCTGTTAACAGACTTTAATGGAAAT 5657 TTTCCATTAAAGTCTGTTG CAACAGACTTTAATGGAAA 5658TTCCATTAAAGTCTGTTGT ACAACAGACTTTAATGGAA 5659 TCCATTAAAGTCTGTTGTTAACAACAGACTTTAATGGA 5660 CCATTAAAGTCTGTTGTTT AAACAACAGACTTTAATGG 5661CATTAAAGTCTGTTGTTTT AAAACAACAGACTTTAATG 5662 ATTAAAGTCTGTTGTTTTGCAAAACAACAGACTTTAAT 5663 TTAAAGTCTGTTGTTTTGT ACAAAACAACAGACTTTAA 5664TAAAGTCTGTTGTTTTGTG CACAAAACAACAGACTTTA

TABLE 2 Human and Mouse Hairless Polymorphisms mRNA Accession PostionGene (bp) number (nt) From/To Comments Human 5699 NM_005144 867 C/A Homosapiens Hairless 1330 T/G hairless 1677 C/T homolog 1686 C/T (mouse)(HR), 2437 C/A transcript 2491 G/A variant 1, 2671 G/A mRNA 2672 C/T2786 T/C 3058 T/C 3064 A/G 3208 C/T 3253 G/A 3340 G/A 3695 C/T 3812 A/T3851 C/T 3854 C/T 4545 A/G 4715 C/G 4820 C/A Mouse 5599 NM_021877 402A/G Mus musculus hairless 535 C/A hairless (hr), 1603 G/A mRNA 1681 A/G1895 C/T 2251 G/A 2482 T/C 2569 T/C 2917 T/C 3232 C/T 3371 A/T 3610 C/A4065 T/G

TABLE 3 Exemplary siRNA target sequences in mammalian hairless mRNAs(shown as cDNA sequences) Start Sequence Region Mouse (Mus musculus)hairless (hr), mRNA, NM_021877 2023 GCAGGAGACACCGGAGACAATCATA ORF (SEQID NO:11373) 2495 GGACTCTTCAACACCCACTGGAGAT ORF (SEQ ID NO:11374) 2713CCAAGTCTGGGCCAAGTTTGACATT ORF (SEQ ID NO:11375) 2831CCACAACCTTCCTGCAATGGAGATT ORF (SEQ ID NO:11376) 2844GCAATGGAGATTCCAATCGGACCAA ORF (SEQ ID NO:11377) 3042CCAGTGATGACCGCATTACCAACAT ORF (SEQ ID NO:11378) 3085GCAGGTAGTAGAACGGAAGATCCAA ORF (SEQ ID NO:11379) 3750CCTGGTATCGAGCACAGAAAGATTT ORF (SEQ ID NO:11380) 4068GCACAATCAGTGTCACTCAGCACTT ORF (SEQ ID NO:11381) Homo sapiens hairlesshomolog (mouse) (HR), transcript variant 1, mRNA, NM_005144 2151GCGGAACCTGGGTTGTTTGGCTTAA ORF (SEQ ID NO:11382) 2831GGACACATCGATAGGGAACAAGGAT ORF (SEQ ID NO:11383) 3626CCCAACTCCACAACCTTCCTGCAAT ORF (SEQ ID NO:11384) 3796GCCATGAGCGAATACACATGGCCTT ORF (SEQ ID NO:11385) 4092CCTGTGTTGGTGTCAGGGATCCAAA ORF (SEQ ID NO:11386) Rat (Rattus norvegicus)hairless (hr) mRNA, NM-024364 913 CCAAGATTCTAGAGCGAGCTCCCTT ORF (SEQ IDNO:11387) 2045 GGATTCCTGTGCCACTTCTGAGGAA ORF (SEQ ID NO:11388) 2601CCACAACTTTCCTGCAATGGAGATT ORF (SEQ ID NO:11389) 2614GCAATGGAGATTCCAATCGGACCAA ORF (SEQ ID NO:11390) 2729GCTGCTAGCCTCTACAGCTGTCAAA ORF (SEQ ID NO:11391) 2765GCATGAGCGGATTCACATGGCCTTT ORF (SEQ ID NO:11392) 2812CCAGTGATGACCGCATTACCAACAT ORF (SEQ ID NO:11393) 2855GCAGGTAGTAGAACGGAAGATCCAA ORF (SEQ ID NO:11394) 3520CCTGGTACCGAGCACAGAAAGATTT ORF (SEQ ID NO:11395) 3838GCACAATCAGTGTCACTCAGCACTT ORF (SEQ ID NO:11396) Monkey (Macaca mulatto)hairless mRNA, complete cds, AF_361864 1152 GCACTCGGAGCAGTTTGAATGTCCAORF (SEQ ID NO:11397) 1344 GGACACATCGATAGGGAACAAGGAG ORF (SEQ IDNO:11398) 2025 GCACCAGGTCTGGGTCAAGTTTGAT ORF (SEQ ID NO:11399) 2172CCACAGGACCAAGAGCATCAAAGAG ORF (SEQ ID NO:113400) 2605CCTGTGTTGGTGTCAGGGATCCAAA ORF (SEQ ID NO:11401) Pig (Sus scrofa)hairless mRNA, partical cds, AY279972 490 CAGATATGGGCAGCCTATGGTGTGA ORF(SEQ ID NO:11402) 918 CCTGGTAAGCACAGTGAGCATCACT ORF (SEQ ID NO:11403)921 GGTAAGCACAGTGAGCATCACTCAG ORF (SEQ ID NO:11404) 926GCACAGTGAGCATCACTCAGCACTT ORF (SEQ ID NO:11405) 927CACAGTGAGCATCACTCAGCACTTC ORF (SEQ ID NO:11406) Sheep (Ovis aries)hairless mRNA, partial cds, AY130969 366 GGATCCTGAGCATAATGGTGGCCAT ORF(SEQ ID NO:11407) 1140 GCTTACTCGACACTCTGAGCAGTTT ORF (SEQ ID NO:11408)1798 GGACTGTTCAATACCCACTGGAGAT ORF (SEQ ID NO:11409) 1967CCCAGTTTGTCTCCAGTCAGCCTTT ORF (SEQ ID NO:11410) 2016CCAGGTCTGGGTCAAGTTTGACATT ORF (SEQ ID NO:11411)

TABLE 4 Human hairless target/siRNA sequences human hairless NM_005144Loop: 475-615 Loop: 651-752 Loop:  951-1137 Loop: 1968-2183 Loop:2348-2568 Loop: 2769-2806 Loop: 3024-3365 Loop: 3069-3277 Loop:4577-4698 Loop: 3605-3724 Loop: 4861-5079 Loop: 310-436 Loop: 1953-2248Loop:  919-1265 Loop: 4286-4465 Loop: 2373-2555 Loop: 4853-5284 Loop:1916-2288 Loop: 2739-2863 Loop: 4874-5043 Loop: 3047-3318 Loop: 959-1123 Loop: 4477-4534 Loop:  871-1302 Loop: 4325-4459 Loop:4913-5029 Loop:  940-1166 Loop: 1946-2277 Loop: 4086-4199 Loop:5093-5247

TABLE 5 Mouse hairless target/siRNA sequences mouse hairless NM_021877Loop: 318-523 Loop: 2422-2459 Loop: 1870-1913 Loop: 5010-5089 Loop:3614-3736 Loop: 20-23 Loop: 1048-1390 Loop: 1122-1304 Loop: 3434-3550Loop: 3257-3337 Loop: 4272-4504 Loop: 3009-3024 Loop: 4879-4967 Loop:668-845 Loop: 4050-4222 Loop: 1702-1800 Loop: 3364-3567 Loop: 1015-1029Loop: 4730-4780 Loop: 1712-1792 Loop: 4540-4566 Loop: 4070-4135 Loop:1220-1260 Loop: 3579-3701 Loop: 445-459 Loop: 3491-3516 Loop: 205-238Loop: 1691-1926 Loop: 2320-2337 Loop: 896-951 Loop: 2212-2244 Loop:5156-5179 Loop: 2850-3948 Loop: 1141-1201 Loop: 2588-2648 Loop: 403-518Loop: 3370-3407 Loop: 412-510 Loop: 4517-4594 Loop: 659-871 Loop:1087-1103 Loop: 1600-1624 Loop: 4389-4461 Loop: 3423-3561 Loop: 713-812Loop: 176-302 Loop: 1073-1336 Loop: 675-837 Loop: 4395-4417 Loop:1082-1316 Loop: 4152-4215 Loop: 2877-2944

1. A method of human hair removal, comprising applying to a human in anarea comprising hair follicles a double stranded nucleic acid moleculecomprising a sequence of at least a portion of human hairless proteinmRNA and a sequence complementary thereto.
 2. The method of claim 1,wherein inhibition of hair growth in said area persists at least onemonth.
 3. The method of claim 1, further comprising synchronizing hairgrowth cycles for hair follicles in said area.
 4. The method of claim 3,wherein said synchronizing includes hair extraction.
 5. The method ofclaim 1, where said double stranded nucleic acid comprises at least one3′-overhang.
 6. The method of claim 5, wherein said 3′-overhang is a 2-or 3′-base overhang.
 7. The method of claim 5, wherein said 3′-overhangcomprises at least one deoxynucleotide.
 8. The method of claim 1,wherein at least one strand of said double stranded nucleic acidcomprises at least one nucleotide analog or internucleotidic linkagedifferent from unmodified RNA.
 9. The method of claim 1, wherein saiddouble stranded nucleic acid molecule comprises the RNA sense sequenceof Oligonucleotide 131, namely 5′-CUCUCCAGACAUUUGGCAA-3′ (SEQ IDNO:11329), and its complementary RNA sequence 5′-TTGCCAAATGTCTGGAGAG-3′(SEQ ID NO:262), wherein said double stranded nucleic acid moleculeinduces RNA interference in a cell in vitro.
 10. The method of claim 1,wherein said double stranded nucleic acid molecule comprises the RNAsense sequence of Oligonucleotide 1194, namely 5′-GUGCGGCCGAUCCGCGCCG-3′(SEQ ID NO: 11330), and its complementary RNA sequence5′-CGGCGCGGAUCGGCCGCAC-3′ (SEQ ID NO: 11331), wherein said doublestranded nucleic acid molecule induces RNA interference in a cell invitro.
 11. The method of claim 1, wherein said double stranded nucleicacid molecule comprises an RNA sense sequence and a complementary RNAantisense sequence selected from the group consisting ofoligonucleotides 1-5664.
 12. The method of claim 11, wherein said sensesequence and said antisense sequence comprises 19 complementarynucleotides and 1 to 3 non-complementary 3′-nucleotides.
 13. The methodof claim 11, wherein said sense sequence and said antisense sequencecomprises 20 complementary nucleotides and 1 to 3 non-complementary3′-nucleotides.
 14. The method of claim 11, wherein said sense sequenceand said antisense sequence comprises 21 complementary nucleotides and 1to 3 non-complementary 3′-nucleotides.
 15. The method of claim 11,wherein said sense sequence and said antisense sequence comprises 22complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.16. The method of claim 11, wherein said sense sequence and saidantisense sequence comprises 23 complementary nucleotides and 1 to 3non-complementary 3′-nucleotides.
 17. The method of claim 11, whereinsaid sense sequence and said antisense sequence comprises 24complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.18. The method of claim 11, wherein said sense sequence and saidantisense sequence comprises 25 complementary nucleotides and 1 to 3non-complementary 3′-nucleotides.
 19. The method of claim 11, whereinsaid sense sequence and said antisense sequence comprises 26complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.20. The method of claim 11, wherein said sense sequence and saidantisense sequence comprises 27 complementary nucleotides and 1 to 3non-complementary 3′-nucleotides.
 21. The method of claim 11, whereinsaid sense sequence and said antisense sequence comprises 28complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.22. A method for hair removal from an area of a mammal comprising hairfollicles, comprising contacting hair follicles in said region with acomposition comprising at least one double stranded nucleic acidmolecule able to inhibit hairless mRNA translation.
 23. The method ofclaim 22, further comprising synchronizing hair growth cycles for hairfollicles in said area.
 24. The method of claim 23, wherein saidsynchronizing comprises extraction of hair in said area.
 25. The methodof claim 22, wherein said mammal is a human.
 26. The method of claim 22,wherein said mammal is a mouse.
 27. The method of claim 22, wherein saidmammal is a rat.
 28. The method of claim 22, wherein said mammal is abovine.
 29. The method of claim 22, wherein inhibition of hair growth insaid area persists at least one month.
 30. The method of claim 22 wheresaid double stranded nucleic acid comprises at least one 3′-overhang.31. The method of claim 30 wherein said 3′-overhang is a 2- or 3′-baseoverhang.
 32. The method of claim 31 wherein said 3′-overhang comprisesat least one deoxynucleotide.
 33. The method of claim 22, wherein atleast one strand of said double stranded nucleic acid comprises at leastone nucleotide analog or internucleotidic linkage different fromunmodified RNA.
 34. The method of claim 22, wherein said double strandednucleic acid molecule comprises the RNA sense sequence ofOligonucleotide 131, namely 5′-CUCUCCAGACAUUUGGCAA-3′ (SEQ ID NO:11329),and its complementary RNA sequence 5′-TTGCCAAATGTCTGGAGAG-3′ (SEQ IDNO:262), or the species homology of said sequences, wherein said doublestranded nucleic acid molecule induces RNA interference in a cell invitro.
 35. The method of claim 22, wherein said double stranded nucleicacid molecule comprises the RNA sense sequence of Oligonucleotide 1194,namely 5′-GUGCGGCCGAUCCGCGCCG-3′ (SEQ ID NO:11330), and itscomplementary RNA sequence 5′-CGGCGCGGAUCGGCCGCAC-3′ (SEQ ID NO:11331),or the species homology of said sequences, wherein said double strandednucleic acid molecule induces RNA interference in a cell in vitro. 36.The method of claim 22, wherein said double stranded nucleic acidmolecule comprises an RNA sense sequence and a complementary RNAantisense sequence selected from the group consisting ofoligonucleotides 1-5664 and their respective antisense sequences, or thespecies homology of said sequences.
 37. The method of claim 36, whereinsaid sense sequence and said antisense sequence comprises 19complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.38. The method of claim 36, wherein said sense sequence and saidantisense sequence comprises 20 complementary nucleotides and 1 to 3non-complementary 3′-nucleotides.
 39. The method of claim 36, whereinsaid sense sequence and said antisense sequence comprises 21complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.40. The method of claim 36, wherein said sense sequence and saidantisense sequence comprises 22 complementary nucleotides and 1 to 3non-complementary 3′-nucleotides.
 41. The method of claim 36, whereinsaid sense sequence and said antisense sequence comprises 23complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.42. The method of claim 36, wherein said sense sequence and saidantisense sequence comprises 24 complementary nucleotides and 1 to 3non-complementary 3′-nucleotides.
 43. The method of claim 36, whereinsaid sense sequence and said antisense sequence comprises 25complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.44. The method of claim 36, wherein said sense sequence and saidantisense sequence comprises 26 complementary nucleotides and 1 to 3non-complementary 3′-nucleotides.
 45. The method of claim 36, whereinsaid sense sequence and said antisense sequence comprises 27complementary nucleotides and 1 to 3 non-complementary 3′-nucleotides.46. The method of claim 36, wherein said sense sequence and saidantisense sequence comprises 28 complementary nucleotides and 1 to 3non-complementary 3′-nucleotides.
 47. A method of inhibiting expressionof hairless protein in a mammal, comprising administering to said mammala double stranded nucleic acid molecule, wherein said double strandednucleic acid molecule comprises a sequence selected from the groupconsisting of oligonucleotides 1-5664 and their respective antisensesequences, or the species homology of said sequences, and a sequencecomplementary thereto.
 48. A method for treating a human desirous oflosing hair, comprising administering to said human a compositioncomprising a double stranded nucleic acid molecule comprising a sequenceof at least a portion of human hairless protein mRNA and a sequencecomplementary thereto.
 49. The method of claim 48, wherein said doublestranded nucleic acid molecule comprises a sequence selected from thegroup consisting of Oligonucleotides 1-5664 and their respectiveantisense sequences, wherein said double stranded nucleic acid moleculeinduces RNA interference in vitro.
 50. A method for marketing acomposition for hair removal, comprising providing for sale to medicalpractitioners or to the public a packaged pharmaceutical compositioncomprising a double stranded nucleic acid molecule comprising a sequenceof at least a portion of human hairless protein mRNA and a sequencecomplementary thereto; and a package label or insert indicating thatsaid pharmaceutical composition can be used for hair removal.
 51. Themethod of claim 50, wherein said pharmaceutical composition is approvedby the U.S. Food and Drug Administration for hair removal in humans. 52.The method of claim 51, wherein said pharmaceutical composition ispackaged with a hair removal wax or other component adapted for hairremoval.
 53. An isolated double stranded nucleic acid molecule,comprising a nucleotide sequence corresponding to 19-25 contiguousnucleotides from human hairless mRNA, wherein said nucleotide sequencecomprises a nucleotide sequence selected from the group consisting ofoligonucleotides 1-5664; and a nucleotide sequence complementarythereto, wherein said double stranded nucleic acid molecule induces RNAinterference in a human cell in vitro.
 54. A pharmaceutical compositioncomprising a double stranded nucleic acid molecule comprising anucleotide sequence corresponding to 19-25 contiguous nucleotides fromhuman hairless mRNA, wherein said nucleotide sequence comprises anucleotide sequence selected from the group consisting ofoligonucleotides 1-5664, and a sequence complementary thereto, whereinsaid double stranded nucleic acid molecule induces RNA interference in ahuman cell in vitro.
 55. A kit comprising a pharmaceutical composition adouble stranded nucleic acid molecule comprising a sequence of at leasta portion of human hairless protein mRNA and a sequence complementarythereto; and a package label or insert indicating that saidpharmaceutical composition can be used for hair removal.
 56. The kit ofclaim 55, wherein said kit is approved by the U.S. Food and DrugAdministration for human hair removal.